Plasmacytoid dendritic cells (pDCs) are antigen-presenting cells that develop into type-I interfe... more Plasmacytoid dendritic cells (pDCs) are antigen-presenting cells that develop into type-I interferon (IFN-I)–producing cells in response to pathogens. Their role in human immunodeficiency virus (HIV) pathogenesis needs to be understood. We analyzed their dynamics in relation to innate and adaptive immunity very early during the acute phase of simian immuno-deficiency virus (SIV) infection in 18 ma-caques. pDC counts decreased in blood and increased in peripheral lymph nodes, consistent with early recruitment in sec-ondary lymphoid tissues. These changes correlated with the kinetic and intensity
The early immune response fails to prevent the establishment of chronic human immunodeficiency vi... more The early immune response fails to prevent the establishment of chronic human immunodeficiency virus (HIV) infection but may influence viremia during primary infection, thereby possibly affecting long-term disease progression. CD25 + FoxP3 + regulatory T cells may contribute to HIV/simian immunodeficiency virus (SIV) pathogenesis by suppressing efficient antiviral responses during primary infection, favoring high levels of viral replication and the establishment of chronic infection. In contrast, they may decrease immune activation during chronic infection. CD4 + regulatory T cells have been studied in the most detail, but CD8 + CD25 + FoxP3 + T cells also have regulatory properties. We monitored the dynamics of CD25 + FoxP3 + T cells during primary and chronic SIVmac251 infection in cynomolgus macaques. The number of peripheral CD4 + CD25 + FoxP3 + T cells paralleled that of memory CD4 + T cells, with a rapid decline during primary infection followed by a rebound to levels just bel...
Cellular immune responses make an important contribution to both the control of human immunodefic... more Cellular immune responses make an important contribution to both the control of human immunodeficiency virus (HIV) replication and disease progression. We used a pathogenic model of SIVmac251 infection of cynomolgus macaques to longitudinally evaluate cellular immune responses in association with various rates of disease progression. We found an inverse relationship between plasma viral load and the simian immunodeficiency virus (SIV)-specific T cells responses in peripheral blood and lymph nodes. SIV-specific T-cell responses in peripheral blood were transient during primary infection, with the highest responses detected around 3 months after infection. There was also a transient increase of central memory CD8 + T cells in peripheral blood during primary infection, and effector memory T-cell counts in peripheral lymph nodes were increased. This study emphasizes the importance of the early virus-specific immune responses in the outcome of HIV/SIV disease and provides details about t...
Plasmacytoid dendritic cells (pDCs) are antigen-presenting cells that develop into type-I interfe... more Plasmacytoid dendritic cells (pDCs) are antigen-presenting cells that develop into type-I interferon (IFN-I)–producing cells in response to pathogens. Their role in human immunodeficiency virus (HIV) pathogenesis needs to be understood. We analyzed their dynamics in relation to innate and adaptive immunity very early during the acute phase of simian immunodeficiency virus (SIV) infection in 18 macaques. pDC counts decreased in blood and increased in peripheral lymph nodes, consistent with early recruitment in secondary lymphoid tissues. These changes correlated with the kinetic and intensity of viremia and were associated with a peak of plasma IFN-I. IFN-I and viremia were positively correlated with functional activity of the immune suppression associated enzyme indoleamine-2,3-dioxygenase (IDO) and FoxP3+CD8+ T cells, which both negatively correlated with SIV-specific T-cell proliferation and CD4+ T-cell activation. These data suggest that pDCs and IFN-I play a key role in shaping ...
HIV/simian immunodeficiency virus (SIV) infection is characterized by progressive CD4(+) T-cell d... more HIV/simian immunodeficiency virus (SIV) infection is characterized by progressive CD4(+) T-cell depletion and immune exhaustion. CD25(+)FoxP3(+) regulatory T cells were evidenced in HIV/SIV infection and disease. They could be positive by suppressing immune activation during chronic infection and/or damper T-cell immunity. Here we evaluated the correlation between regulatory T-cell function and disease progression in pathogenic SIV infection. We compared the in-vitro suppressive capacity of CD25(+) cells from peripheral blood and peripheral lymph nodes of 18 SIVmac251-infected cynomolgus macaques to look for correlates with biological markers of progression to disease. The in-vitro suppressive capacity of CD25(+) cells was evaluated in a proliferation assay. Ex-vivo T-cell activation was determined by phenotypic labeling followed by flow cytometry. In chronic infection, CD25(+) regulatory T-cell activity correlated to preserved CD4 T-cell counts and lower T-cell activation. This study suggests that regulatory T-cell function is lost during disease progression and may have a positive impact on HIV/SIV disease.
Plasmacytoid dendritic cells (pDCs) are antigen-presenting cells that develop into type-I interfe... more Plasmacytoid dendritic cells (pDCs) are antigen-presenting cells that develop into type-I interferon (IFN-I)–producing cells in response to pathogens. Their role in human immunodeficiency virus (HIV) pathogenesis needs to be understood. We analyzed their dynamics in relation to innate and adaptive immunity very early during the acute phase of simian immuno-deficiency virus (SIV) infection in 18 ma-caques. pDC counts decreased in blood and increased in peripheral lymph nodes, consistent with early recruitment in sec-ondary lymphoid tissues. These changes correlated with the kinetic and intensity
The early immune response fails to prevent the establishment of chronic human immunodeficiency vi... more The early immune response fails to prevent the establishment of chronic human immunodeficiency virus (HIV) infection but may influence viremia during primary infection, thereby possibly affecting long-term disease progression. CD25 + FoxP3 + regulatory T cells may contribute to HIV/simian immunodeficiency virus (SIV) pathogenesis by suppressing efficient antiviral responses during primary infection, favoring high levels of viral replication and the establishment of chronic infection. In contrast, they may decrease immune activation during chronic infection. CD4 + regulatory T cells have been studied in the most detail, but CD8 + CD25 + FoxP3 + T cells also have regulatory properties. We monitored the dynamics of CD25 + FoxP3 + T cells during primary and chronic SIVmac251 infection in cynomolgus macaques. The number of peripheral CD4 + CD25 + FoxP3 + T cells paralleled that of memory CD4 + T cells, with a rapid decline during primary infection followed by a rebound to levels just bel...
Cellular immune responses make an important contribution to both the control of human immunodefic... more Cellular immune responses make an important contribution to both the control of human immunodeficiency virus (HIV) replication and disease progression. We used a pathogenic model of SIVmac251 infection of cynomolgus macaques to longitudinally evaluate cellular immune responses in association with various rates of disease progression. We found an inverse relationship between plasma viral load and the simian immunodeficiency virus (SIV)-specific T cells responses in peripheral blood and lymph nodes. SIV-specific T-cell responses in peripheral blood were transient during primary infection, with the highest responses detected around 3 months after infection. There was also a transient increase of central memory CD8 + T cells in peripheral blood during primary infection, and effector memory T-cell counts in peripheral lymph nodes were increased. This study emphasizes the importance of the early virus-specific immune responses in the outcome of HIV/SIV disease and provides details about t...
Plasmacytoid dendritic cells (pDCs) are antigen-presenting cells that develop into type-I interfe... more Plasmacytoid dendritic cells (pDCs) are antigen-presenting cells that develop into type-I interferon (IFN-I)–producing cells in response to pathogens. Their role in human immunodeficiency virus (HIV) pathogenesis needs to be understood. We analyzed their dynamics in relation to innate and adaptive immunity very early during the acute phase of simian immunodeficiency virus (SIV) infection in 18 macaques. pDC counts decreased in blood and increased in peripheral lymph nodes, consistent with early recruitment in secondary lymphoid tissues. These changes correlated with the kinetic and intensity of viremia and were associated with a peak of plasma IFN-I. IFN-I and viremia were positively correlated with functional activity of the immune suppression associated enzyme indoleamine-2,3-dioxygenase (IDO) and FoxP3+CD8+ T cells, which both negatively correlated with SIV-specific T-cell proliferation and CD4+ T-cell activation. These data suggest that pDCs and IFN-I play a key role in shaping ...
HIV/simian immunodeficiency virus (SIV) infection is characterized by progressive CD4(+) T-cell d... more HIV/simian immunodeficiency virus (SIV) infection is characterized by progressive CD4(+) T-cell depletion and immune exhaustion. CD25(+)FoxP3(+) regulatory T cells were evidenced in HIV/SIV infection and disease. They could be positive by suppressing immune activation during chronic infection and/or damper T-cell immunity. Here we evaluated the correlation between regulatory T-cell function and disease progression in pathogenic SIV infection. We compared the in-vitro suppressive capacity of CD25(+) cells from peripheral blood and peripheral lymph nodes of 18 SIVmac251-infected cynomolgus macaques to look for correlates with biological markers of progression to disease. The in-vitro suppressive capacity of CD25(+) cells was evaluated in a proliferation assay. Ex-vivo T-cell activation was determined by phenotypic labeling followed by flow cytometry. In chronic infection, CD25(+) regulatory T-cell activity correlated to preserved CD4 T-cell counts and lower T-cell activation. This study suggests that regulatory T-cell function is lost during disease progression and may have a positive impact on HIV/SIV disease.
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Papers by Benoît Malleret