Efficient TCR repertoire selection in the thymus is critical for immune function, ensuring the pr... more Efficient TCR repertoire selection in the thymus is critical for immune function, ensuring the production of functional MHC-restricted and self-tolerant T cells. T cell education in the thymus involves positive and negative selection processes where apoptosis play an especially important role in eliminating useless or potentially dangerous thymocytes. For decades, positive and negative selection in T cell development has attracted the attention and considerable research has been conducted to improve our understanding of how ligand induced signaling through the T cell receptor (TCR) can lead to both: rescue from death in the case of positive selection and death in the case of negative selection. In this brief report, we review the basic concepts involved in the extrinsic and intrinsic pathway of apoptosis, and provide an overview of the events that leads immature T cells to survive or die by apoptosis during their intrathymic development.
Revista do Instituto de Medicina Tropical de São Paulo, 1994
The possibility that some virus contaminants could be altering host response to Trypanosoma cruzi... more The possibility that some virus contaminants could be altering host response to Trypanosoma cruzi experimental infection was investigated. Data obtained showed that CBA/J mice infected with stocks of parasite maintained in mice (Y1UEC) presented higher level of parasitemia and shorter survival times than those infected with a stock (Y1TC) which was also maintained in mice but had been previously passaged in cell culture. Mouse antibody production tests, performed with the filtered plasma of mice infected with Y1UEC, indicated the presence of mouse hepatitis virus (MHV) while no virus was detected when testing the plasma of Y1TC infected mice. Filtered plasma of Y1EUC infected mice was shown to contain a factor able to enhance the level of parasitemia and to reduce the mean survival time of mice challenged with 10(5) Y1TC. This factor, that could be serially passaged to naïve mice was shown to be a coronavirus by neutralization tests.
Neutrophils (PMN) play a central role in host defense against the neglected fungal infection para... more Neutrophils (PMN) play a central role in host defense against the neglected fungal infection paracoccidioidomycosis (PCM), which is caused by the dimorphic fungus Paracoccidioides brasiliensis (Pb). PCM is of major importance, especially in Latin America, and its treatment relies on the use of antifungal drugs. However, the course of treatment is lengthy, leading to side effects and even development of fungal resistance. The goal of the study was to use low-level laser therapy (LLLT) to stimulate PMN to fight Pb in vivo. Swiss mice with subcutaneous air pouches were inoculated with a virulent strain of Pb or fungal cell wall components (Zymosan), and then received LLLT (780 nm; 50 mW; 12.5 J/cm2; 30 seconds per point, giving a total energy of 0.5 J per point) on alternate days at two points on each hind leg. The aim was to reach the bone marrow in the femur with light. Non-irradiated animals were used as controls. The number and viability of the PMN that migrated to the inoculation site was assessed, as well as their ability to synthesize proteins, produce reactive oxygen species (ROS) and their fungicidal activity. The highly pure PMN populations obtained after 10 days of infection were also subsequently cultured in the presence of Pb for trials of protein production, evaluation of mitochondrial activity, ROS production and quantification of viable fungi growth. PMN from mice that received LLLT were more active metabolically, had higher fungicidal activity against Pb in vivo and also in vitro. The kinetics of neutrophil
The thymus plays an important role shaping the T cell repertoire in the periphery, partly, throug... more The thymus plays an important role shaping the T cell repertoire in the periphery, partly, through the elimination of inflammatory auto-reactive cells. It has been shown that, during Plasmodium berghei infection, the thymus is rendered atrophic by the premature egress of CD4 + CD8 + double-positive (DP) T cells to the periphery. To investigate whether autoimmune diseases are affected after Plasmodium berghei NK65 infection, we immunized C57BL/6 mice, which was previously infected with P.berghei NK65 and treated with chloroquine (CQ), with MOG 35-55 peptide and the clinical course of Experimental Autoimmune Encephalomyelitis (EAE) was evaluated. Our results showed that NK65+CQ+EAE mice developed a more severe disease than control EAE mice. The same pattern of disease severity was observed in MOG 35-55-immunized mice after adoptive transfer of P.berghei-elicited splenic DP-T cells. The higher frequency of IL-17 +-and IFN-c +-producing DP lymphocytes in the Central Nervous System of these mice suggests that immature lymphocytes contribute to disease worsening. To our knowledge, this is the first study to integrate the possible relationship between malaria and multiple sclerosis through the contribution of the thymus. Notwithstanding, further studies must be conducted to assert the relevance of malaria-induced thymic atrophy in the susceptibility and clinical course of other inflammatory autoimmune diseases.
Many works have shown that immunosuppressive effects induced by systemic mycosis can be related t... more Many works have shown that immunosuppressive effects induced by systemic mycosis can be related to primary lymphoid organ damage. Previous studies in our laboratory showed that Paracoccidioides brasiliensis was able to invade the thymus, inducing a severe atrophy with significant reduction of cortical area along with a loss of cortico-medullary boundary. The objective of the present study was to investigate whether thymic atrophy is caused by programmed cell death (PCD) and to examine the ultrastructural characteristics of the thymus in experimentally infected BALB/c mice. The results revealed an eightfold increase in the apoptotic index occurring by day 5 post infection, i.e., during early stages of the infection, shown by immunohistochemistry. In addition, typical cell alterations of autophagic PCD were observed by transmission electron microscopy. Taken together, these results reinforce the idea that thymic alterations may be involved in the immunosuppressive phenomenon frequently associated with paracoccidioidomycotic infection.
Journal of Photochemistry and Photobiology B: Biology, 2006
Paracoccidioidomycosis (PCM) is the most prevalent human mycosis in Latin America. The infection ... more Paracoccidioidomycosis (PCM) is the most prevalent human mycosis in Latin America. The infection is thought to take place firstly in the lungs and then may disseminate to other organs and tissues. Treatment by currently available antifungals is lengthy, the drugs may have undesirable side effects, and some are costly. Occasional resistant strains of Paracoccidioides brasiliensis, the causative agent of PCM, have been reported. So, the search for more efficient treatments or adjuvant therapies has to be continued. In this work, we evaluated the effects of HeNe laser irradiation on cutaneous inflammatory lesions caused by the inoculation of 5 • 10 6 /0.1 ml yeasts cells into the back footpad of Balb/c mice. HeNe irradiation (k = 632.8 nm, 3 mW, incident energy of 3 J/cm 2) was applied at days 7, 8 and 9 postinfection and histological and immunohistochemical analysis were done. Unirradiated animals were used as controls. The results showed that laser-treated mice presented reduction of footpad edema, faster cutaneous wound healing, confluent granuloma, diffuse-and more loosely distributed immunolabeling for TNF-a, enhanced labeling of IFN-c and any P. brasiliensis form detected, whereas multiple viable fungi were seen in diffuse widespread granulomas obtained from non-treated mice foot-pad. Fungi that were harvested from lasertreated animals presented no capability of growth in vitro as compared to those obtained from non-treated mice. We conclude that HeNe laser irradiation was able to inhibit the progress of inflammatory local reaction produced by P. brasiliensis infection and influence local cytokines production. We suggest that this treatment modality can be a useful coadjuvant tool to be combined with antifungal agents in the treatment of PCM ulcerations. The mechanisms involved in laser therapy of PCM lesions need further investigation.
We have previously showed alterations in the thymus during experimental infection with Plasmodium... more We have previously showed alterations in the thymus during experimental infection with Plasmodium berghei, the causative agent of Malaria. Such alterations comprised histological changes with loss of delimitation between cortical and medullar regions, a profound atrophy with depletion of CD4(+)CD8(+) double-positive (DP) thymocytes, and severe changes in the expression of cell migration-related molecules, belonging to the extracellular matrix and chemokine protein families. Taken together, these considerations prompted us to evaluate if the acute thymic atrophy observed during Plasmodium infection was correlated with increased apoptotic levels of thymocytes or with their premature emigration to the periphery. Our results confirmed that the marked reduction of the thymus weight in infected animals was accompanied by histological alterations, which included a very large number of cells showing nuclear condensation and karyorrhectic changes surrounded by histiocytes suggesting increased levels of apoptosis. This was confirmed by immunohistochemistry and flow cytometry techniques. In order to verify if an accelerated emigration of thymic cells to the peripheral lymphoid organs was also occurring we analyzed the spleen and mesenteric lymph nodes from control and infected mice. No significant differences were found in the spleen, but were seen after 14 days of infection between control and infected mice in the mesenteric lymph nodes. The main alteration was the presence of double negative (CD4(-)CD8(-)) and double positive (CD4(+)CD8(+)) cells. We concluded that both apoptosis of thymocytes and premature egress of immature cells take place during infection. Additional studies will be necessary to verify how such alterations might influence the systemic immune response to the parasite.
Chloroquine (CQ), an antimalarial drug, has been shown to modulate the immune system and reduce t... more Chloroquine (CQ), an antimalarial drug, has been shown to modulate the immune system and reduce the severity of experimental autoimmune encephalomyelitis (EAE). The mechanisms of disease suppression are dependent on regulatory T cell induction, although Tregs-independent mechanisms exist. We aimed to evaluate whether CQ is capable to modulate bone marrow-derived dendritic cells (DCs) both phenotypically and functionally as well as whether transfer of CQ-modulated DCs reduces EAE course. Our results show that CQ-treated DCs presented altered ultrastructure morphology and lower expression of molecules involved in antigen presentation. Consequently, T cell proliferation was diminished in coculture experiments. When transferred into EAE mice, DC-CQ was able to reduce the clinical manifestation of the disease through the modulation of the immune response against neuroantigens. The data presented herein indicate that chloroquine-mediated modulation of the immune system is achieved by a direct effect on DCs and that DC-CQ adoptive transfer may be a promising approach for avoiding drug toxicity.
Literature has shown that immunosuppression observed in systemic mycosis can be related to damage... more Literature has shown that immunosuppression observed in systemic mycosis can be related to damage in primary lymphoid organs. We have studied the immunopathological alterations induced experimentally by Paracoccidioides brasiliensis in these organs. In this work, thymic alterations induced in BALB/c mice during acute and chronic stages of infection are described. It was observed that P. brasiliensis is able to invade the thymic microenvironment, inducing severe atrophy characterized by degeneration of the cortical area, organ weight decrease, loss of corticomedullary delimitation and increase in histiocyte number. Occurrence of polymorphonuclear infiltration in the subcapsular area was also observed. Our results demonstrate that P. brasiliensis induces profound thymic atrophy and raises the question of whether this could be a fungal strategy to achieve successful establishment in the host over the long term.
The effect of sub-lethal doses of coronaviruses on the course of disease in CBA mice experimental... more The effect of sub-lethal doses of coronaviruses on the course of disease in CBA mice experimentally infected with a mildly pathogenic strain of Trypanosoma cruzi was investigated. Mice were inoculated with either T. cruzi, 0.1 median lethal dose (LD50) of coronavirus (mouse hepatitis virus [MHV-3] or virus X), or both pathogens. Levels of parasitemia, mortality, and the extent of pathologic alterations in lymphoid organs were determined. Mice inoculated with T. cruzi had mild alterations in their lymphoid organs and survived infection. In contrast, mice inoculated with both pathogens died, and had significantly higher levels of parasitemia and profound alterations in lymphoid organs. These results indicate that the pathologic profile of T. cruzi infection can be profoundly altered by subclinical infection with coronaviruses.
operated by two important regulators, the ER calcium sensor Stim and the CRAC channel, Orai. Mamm... more operated by two important regulators, the ER calcium sensor Stim and the CRAC channel, Orai. Mammalian STIM1 and STIM2 sense ER calcium levels through a calcium-binding EF-hand located in the ER lumen. We generated conditional Stim1, Stim2 knockout mice and showed that SOCE is essential for effector functions of peripheral T cells using CD4Cre transgenic mice. We further showed that SOCE is important for regulatory T cell development and function. To investigate the roles of SOCE in all T-lineage cells, we have generated mice with a VaviCre-or LckCre-mediated deletion of the Stim1 and Stim2 genes. We show that the complete absence of SOCE did not affect conventional ab+ TCR T cell development. Positive selection is also normal. In contrast, the development of regulatory T cells and invariant NKT (iNKT) cells was impaired in these mice. Among them, iNKT cell development was most sensitive to the loss of SOCE since the number of iNKT cells was substantially decreased in STIM1-deficeint mice. In addition, overexpression of STIM2 could restore the number of regulatory T cells but not iNKT cells. Taken together, we conclude that store-operated calcium entry is crucial for the development of regulatory T cells and iNKT cells, but dispensable for the development of conventional ab+ TCR T cells.
respectively). The funders had no role in study inflammation) and stimulation of regulatory T cel... more respectively). The funders had no role in study inflammation) and stimulation of regulatory T cells (in chronic inflammation). New studies must be conducted in order to assess the possible use of viola in therapeutic approaches in human autoimmune diseases.
Efficient TCR repertoire selection in the thymus is critical for immune function, ensuring the pr... more Efficient TCR repertoire selection in the thymus is critical for immune function, ensuring the production of functional MHC-restricted and self-tolerant T cells. T cell education in the thymus involves positive and negative selection processes where apoptosis play an especially important role in eliminating useless or potentially dangerous thymocytes. For decades, positive and negative selection in T cell development has attracted the attention and considerable research has been conducted to improve our understanding of how ligand induced signaling through the T cell receptor (TCR) can lead to both: rescue from death in the case of positive selection and death in the case of negative selection. In this brief report, we review the basic concepts involved in the extrinsic and intrinsic pathway of apoptosis, and provide an overview of the events that leads immature T cells to survive or die by apoptosis during their intrathymic development.
Revista do Instituto de Medicina Tropical de São Paulo, 1994
The possibility that some virus contaminants could be altering host response to Trypanosoma cruzi... more The possibility that some virus contaminants could be altering host response to Trypanosoma cruzi experimental infection was investigated. Data obtained showed that CBA/J mice infected with stocks of parasite maintained in mice (Y1UEC) presented higher level of parasitemia and shorter survival times than those infected with a stock (Y1TC) which was also maintained in mice but had been previously passaged in cell culture. Mouse antibody production tests, performed with the filtered plasma of mice infected with Y1UEC, indicated the presence of mouse hepatitis virus (MHV) while no virus was detected when testing the plasma of Y1TC infected mice. Filtered plasma of Y1EUC infected mice was shown to contain a factor able to enhance the level of parasitemia and to reduce the mean survival time of mice challenged with 10(5) Y1TC. This factor, that could be serially passaged to naïve mice was shown to be a coronavirus by neutralization tests.
Neutrophils (PMN) play a central role in host defense against the neglected fungal infection para... more Neutrophils (PMN) play a central role in host defense against the neglected fungal infection paracoccidioidomycosis (PCM), which is caused by the dimorphic fungus Paracoccidioides brasiliensis (Pb). PCM is of major importance, especially in Latin America, and its treatment relies on the use of antifungal drugs. However, the course of treatment is lengthy, leading to side effects and even development of fungal resistance. The goal of the study was to use low-level laser therapy (LLLT) to stimulate PMN to fight Pb in vivo. Swiss mice with subcutaneous air pouches were inoculated with a virulent strain of Pb or fungal cell wall components (Zymosan), and then received LLLT (780 nm; 50 mW; 12.5 J/cm2; 30 seconds per point, giving a total energy of 0.5 J per point) on alternate days at two points on each hind leg. The aim was to reach the bone marrow in the femur with light. Non-irradiated animals were used as controls. The number and viability of the PMN that migrated to the inoculation site was assessed, as well as their ability to synthesize proteins, produce reactive oxygen species (ROS) and their fungicidal activity. The highly pure PMN populations obtained after 10 days of infection were also subsequently cultured in the presence of Pb for trials of protein production, evaluation of mitochondrial activity, ROS production and quantification of viable fungi growth. PMN from mice that received LLLT were more active metabolically, had higher fungicidal activity against Pb in vivo and also in vitro. The kinetics of neutrophil
The thymus plays an important role shaping the T cell repertoire in the periphery, partly, throug... more The thymus plays an important role shaping the T cell repertoire in the periphery, partly, through the elimination of inflammatory auto-reactive cells. It has been shown that, during Plasmodium berghei infection, the thymus is rendered atrophic by the premature egress of CD4 + CD8 + double-positive (DP) T cells to the periphery. To investigate whether autoimmune diseases are affected after Plasmodium berghei NK65 infection, we immunized C57BL/6 mice, which was previously infected with P.berghei NK65 and treated with chloroquine (CQ), with MOG 35-55 peptide and the clinical course of Experimental Autoimmune Encephalomyelitis (EAE) was evaluated. Our results showed that NK65+CQ+EAE mice developed a more severe disease than control EAE mice. The same pattern of disease severity was observed in MOG 35-55-immunized mice after adoptive transfer of P.berghei-elicited splenic DP-T cells. The higher frequency of IL-17 +-and IFN-c +-producing DP lymphocytes in the Central Nervous System of these mice suggests that immature lymphocytes contribute to disease worsening. To our knowledge, this is the first study to integrate the possible relationship between malaria and multiple sclerosis through the contribution of the thymus. Notwithstanding, further studies must be conducted to assert the relevance of malaria-induced thymic atrophy in the susceptibility and clinical course of other inflammatory autoimmune diseases.
Many works have shown that immunosuppressive effects induced by systemic mycosis can be related t... more Many works have shown that immunosuppressive effects induced by systemic mycosis can be related to primary lymphoid organ damage. Previous studies in our laboratory showed that Paracoccidioides brasiliensis was able to invade the thymus, inducing a severe atrophy with significant reduction of cortical area along with a loss of cortico-medullary boundary. The objective of the present study was to investigate whether thymic atrophy is caused by programmed cell death (PCD) and to examine the ultrastructural characteristics of the thymus in experimentally infected BALB/c mice. The results revealed an eightfold increase in the apoptotic index occurring by day 5 post infection, i.e., during early stages of the infection, shown by immunohistochemistry. In addition, typical cell alterations of autophagic PCD were observed by transmission electron microscopy. Taken together, these results reinforce the idea that thymic alterations may be involved in the immunosuppressive phenomenon frequently associated with paracoccidioidomycotic infection.
Journal of Photochemistry and Photobiology B: Biology, 2006
Paracoccidioidomycosis (PCM) is the most prevalent human mycosis in Latin America. The infection ... more Paracoccidioidomycosis (PCM) is the most prevalent human mycosis in Latin America. The infection is thought to take place firstly in the lungs and then may disseminate to other organs and tissues. Treatment by currently available antifungals is lengthy, the drugs may have undesirable side effects, and some are costly. Occasional resistant strains of Paracoccidioides brasiliensis, the causative agent of PCM, have been reported. So, the search for more efficient treatments or adjuvant therapies has to be continued. In this work, we evaluated the effects of HeNe laser irradiation on cutaneous inflammatory lesions caused by the inoculation of 5 • 10 6 /0.1 ml yeasts cells into the back footpad of Balb/c mice. HeNe irradiation (k = 632.8 nm, 3 mW, incident energy of 3 J/cm 2) was applied at days 7, 8 and 9 postinfection and histological and immunohistochemical analysis were done. Unirradiated animals were used as controls. The results showed that laser-treated mice presented reduction of footpad edema, faster cutaneous wound healing, confluent granuloma, diffuse-and more loosely distributed immunolabeling for TNF-a, enhanced labeling of IFN-c and any P. brasiliensis form detected, whereas multiple viable fungi were seen in diffuse widespread granulomas obtained from non-treated mice foot-pad. Fungi that were harvested from lasertreated animals presented no capability of growth in vitro as compared to those obtained from non-treated mice. We conclude that HeNe laser irradiation was able to inhibit the progress of inflammatory local reaction produced by P. brasiliensis infection and influence local cytokines production. We suggest that this treatment modality can be a useful coadjuvant tool to be combined with antifungal agents in the treatment of PCM ulcerations. The mechanisms involved in laser therapy of PCM lesions need further investigation.
We have previously showed alterations in the thymus during experimental infection with Plasmodium... more We have previously showed alterations in the thymus during experimental infection with Plasmodium berghei, the causative agent of Malaria. Such alterations comprised histological changes with loss of delimitation between cortical and medullar regions, a profound atrophy with depletion of CD4(+)CD8(+) double-positive (DP) thymocytes, and severe changes in the expression of cell migration-related molecules, belonging to the extracellular matrix and chemokine protein families. Taken together, these considerations prompted us to evaluate if the acute thymic atrophy observed during Plasmodium infection was correlated with increased apoptotic levels of thymocytes or with their premature emigration to the periphery. Our results confirmed that the marked reduction of the thymus weight in infected animals was accompanied by histological alterations, which included a very large number of cells showing nuclear condensation and karyorrhectic changes surrounded by histiocytes suggesting increased levels of apoptosis. This was confirmed by immunohistochemistry and flow cytometry techniques. In order to verify if an accelerated emigration of thymic cells to the peripheral lymphoid organs was also occurring we analyzed the spleen and mesenteric lymph nodes from control and infected mice. No significant differences were found in the spleen, but were seen after 14 days of infection between control and infected mice in the mesenteric lymph nodes. The main alteration was the presence of double negative (CD4(-)CD8(-)) and double positive (CD4(+)CD8(+)) cells. We concluded that both apoptosis of thymocytes and premature egress of immature cells take place during infection. Additional studies will be necessary to verify how such alterations might influence the systemic immune response to the parasite.
Chloroquine (CQ), an antimalarial drug, has been shown to modulate the immune system and reduce t... more Chloroquine (CQ), an antimalarial drug, has been shown to modulate the immune system and reduce the severity of experimental autoimmune encephalomyelitis (EAE). The mechanisms of disease suppression are dependent on regulatory T cell induction, although Tregs-independent mechanisms exist. We aimed to evaluate whether CQ is capable to modulate bone marrow-derived dendritic cells (DCs) both phenotypically and functionally as well as whether transfer of CQ-modulated DCs reduces EAE course. Our results show that CQ-treated DCs presented altered ultrastructure morphology and lower expression of molecules involved in antigen presentation. Consequently, T cell proliferation was diminished in coculture experiments. When transferred into EAE mice, DC-CQ was able to reduce the clinical manifestation of the disease through the modulation of the immune response against neuroantigens. The data presented herein indicate that chloroquine-mediated modulation of the immune system is achieved by a direct effect on DCs and that DC-CQ adoptive transfer may be a promising approach for avoiding drug toxicity.
Literature has shown that immunosuppression observed in systemic mycosis can be related to damage... more Literature has shown that immunosuppression observed in systemic mycosis can be related to damage in primary lymphoid organs. We have studied the immunopathological alterations induced experimentally by Paracoccidioides brasiliensis in these organs. In this work, thymic alterations induced in BALB/c mice during acute and chronic stages of infection are described. It was observed that P. brasiliensis is able to invade the thymic microenvironment, inducing severe atrophy characterized by degeneration of the cortical area, organ weight decrease, loss of corticomedullary delimitation and increase in histiocyte number. Occurrence of polymorphonuclear infiltration in the subcapsular area was also observed. Our results demonstrate that P. brasiliensis induces profound thymic atrophy and raises the question of whether this could be a fungal strategy to achieve successful establishment in the host over the long term.
The effect of sub-lethal doses of coronaviruses on the course of disease in CBA mice experimental... more The effect of sub-lethal doses of coronaviruses on the course of disease in CBA mice experimentally infected with a mildly pathogenic strain of Trypanosoma cruzi was investigated. Mice were inoculated with either T. cruzi, 0.1 median lethal dose (LD50) of coronavirus (mouse hepatitis virus [MHV-3] or virus X), or both pathogens. Levels of parasitemia, mortality, and the extent of pathologic alterations in lymphoid organs were determined. Mice inoculated with T. cruzi had mild alterations in their lymphoid organs and survived infection. In contrast, mice inoculated with both pathogens died, and had significantly higher levels of parasitemia and profound alterations in lymphoid organs. These results indicate that the pathologic profile of T. cruzi infection can be profoundly altered by subclinical infection with coronaviruses.
operated by two important regulators, the ER calcium sensor Stim and the CRAC channel, Orai. Mamm... more operated by two important regulators, the ER calcium sensor Stim and the CRAC channel, Orai. Mammalian STIM1 and STIM2 sense ER calcium levels through a calcium-binding EF-hand located in the ER lumen. We generated conditional Stim1, Stim2 knockout mice and showed that SOCE is essential for effector functions of peripheral T cells using CD4Cre transgenic mice. We further showed that SOCE is important for regulatory T cell development and function. To investigate the roles of SOCE in all T-lineage cells, we have generated mice with a VaviCre-or LckCre-mediated deletion of the Stim1 and Stim2 genes. We show that the complete absence of SOCE did not affect conventional ab+ TCR T cell development. Positive selection is also normal. In contrast, the development of regulatory T cells and invariant NKT (iNKT) cells was impaired in these mice. Among them, iNKT cell development was most sensitive to the loss of SOCE since the number of iNKT cells was substantially decreased in STIM1-deficeint mice. In addition, overexpression of STIM2 could restore the number of regulatory T cells but not iNKT cells. Taken together, we conclude that store-operated calcium entry is crucial for the development of regulatory T cells and iNKT cells, but dispensable for the development of conventional ab+ TCR T cells.
respectively). The funders had no role in study inflammation) and stimulation of regulatory T cel... more respectively). The funders had no role in study inflammation) and stimulation of regulatory T cells (in chronic inflammation). New studies must be conducted in order to assess the possible use of viola in therapeutic approaches in human autoimmune diseases.
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