CD56bright and CD56dim NK cell subsets have been proposed to represent either phenotypically and ... more CD56bright and CD56dim NK cell subsets have been proposed to represent either phenotypically and functionally distinct NK cell subsets or, respectively, immature and mature stages of the NK cell lineage. To this regard, using FLT3 ligand, IL-15 and IL-21 cytokine combination, we have recently described the in vitro generation of CD56dim/CD117neg NK cells from CD34+ hematopoietic progenitors, but not from immature CD56bright NK cells (Zamai et al. Cytometry A 2012;81:294-302), suggesting that they represent phenotypically and functionally distinct NK subsets. Based on these observations we have analyzed the NK cells developed in vitro from CD34+ progenitors cultured with FLT3-L plus IL-15 and IL-21, trying to distinguish between the two NK cell subsets. CD56bright /CD117+ NK cells generated after 15 days of culture, early expressed natural cytotoxicity receptors (NCRs), NKG2D, CD161 and CD244, while only a subset expressed granzyme-B, perforin, LFA-1, and CD94- CD159a heterodimer. Di...
Innate lymphoid cells (ILCs) are immune effector cells which, differently from T and B lymphocyte... more Innate lymphoid cells (ILCs) are immune effector cells which, differently from T and B lymphocytes, do not express rearranged receptors. Besides NK cells that belong to the ILC1 group, the novel lineages have raised a question regarding their developmental relationship. To this regard, the ILC groups differ not only for their effector functions but also for their anatomical localization, suggesting the possibility that a common progenitor may migrate and differentiate in different ILCs, depending on the tissue microenvironment. On the other hand, we have recently indicated that CD56dim and CD56bright NK cells, both considered in the ILC1 group, originate from two distinct precursors which generate cells with convergent phenotypes and functions. CD56bright /CD117+ NK cells, differently from CD56dim/CD117neg NK cells, early express natural cytotoxicity receptors (NCRs), while lately upregulate granzyme- B, perforin, LFA-1, and CD94-CD159a heterodimer (1). Within the ILC family, the re...
The NK cell population is characterized by distinct NK cell subsets that respond differently to t... more The NK cell population is characterized by distinct NK cell subsets that respond differently to the various activating stimuli. For this reason, the determination of the optimal cytotoxic activation of the different NK cell subsets can be a crucial aspect to be exploited to counter cancer cells in oncologic patients. To evaluate how the triggering of different combination of activating receptors can affect the cytotoxic responses of different NK cell subsets, we developed a microbead-based degranulation assay. By using this new assay, we were able to detect CD107a+ degranulating NK cells even within the less cytotoxic subsets (i.e., resting CD56bright and unlicensed CD56dim NK cells), thus demonstrating its high sensitivity. Interestingly, signals delivered by the co-engagement of NKp46 with 2B4, but not with CD2 or DNAM-1, strongly cooperate to enhance degranulation on both licensed and unlicensed CD56dim NK cells. Of note, 2B4 is known to bind CD48 hematopoietic antigen, therefore...
Although NK cells are considered part of the innate immune system, a series of evidences has demo... more Although NK cells are considered part of the innate immune system, a series of evidences has demonstrated that they possess characteristics typical of the adaptive immune system. These NK adaptive features, in particular their memory-like functions, are discussed from an ontogenetic and evolutionary point of view.
Background. Human Natural killer (NK) cells are characterized by NK cell receptors (NKRs) with in... more Background. Human Natural killer (NK) cells are characterized by NK cell receptors (NKRs) with inhibitory and activatory function that finely control their functional activities. In particular, they express inhibitory receptors for MHC class I molecules, named killer cell immunoglobulin (Ig)-like receptors (KIRs) and C-type lectin CD94-CD159a, and many triggering molecules like NKp30, NKp44, NKp46,(called natural cytotoxicity receptors, NCRs), NKG2D, CD161, and CD244. The majority of peripheral blood human NK cells are ...
CD56bright and CD56dim NK cell subsets have been proposed to represent either phenotypically and ... more CD56bright and CD56dim NK cell subsets have been proposed to represent either phenotypically and functionally distinct NK cell subsets or, respectively, immature and mature stages of the NK cell lineage. To this regard, using FLT3 ligand, IL-15 and IL-21 cytokine combination, we have recently described the in vitro generation of CD56dim/CD117neg NK cells from CD34+ hematopoietic progenitors, but not from immature CD56bright NK cells (Zamai et al. Cytometry A 2012;81:294-302), suggesting that they represent phenotypically and functionally distinct NK subsets. Based on these observations we have analyzed the NK cells developed in vitro from CD34+ progenitors cultured with FLT3-L plus IL-15 and IL-21, trying to distinguish between the two NK cell subsets. CD56bright /CD117+ NK cells generated after 15 days of culture, early expressed natural cytotoxicity receptors (NCRs), NKG2D, CD161 and CD244, while only a subset expressed granzyme-B, perforin, LFA-1, and CD94- CD159a heterodimer. Di...
Innate lymphoid cells (ILCs) are immune effector cells which, differently from T and B lymphocyte... more Innate lymphoid cells (ILCs) are immune effector cells which, differently from T and B lymphocytes, do not express rearranged receptors. Besides NK cells that belong to the ILC1 group, the novel lineages have raised a question regarding their developmental relationship. To this regard, the ILC groups differ not only for their effector functions but also for their anatomical localization, suggesting the possibility that a common progenitor may migrate and differentiate in different ILCs, depending on the tissue microenvironment. On the other hand, we have recently indicated that CD56dim and CD56bright NK cells, both considered in the ILC1 group, originate from two distinct precursors which generate cells with convergent phenotypes and functions. CD56bright /CD117+ NK cells, differently from CD56dim/CD117neg NK cells, early express natural cytotoxicity receptors (NCRs), while lately upregulate granzyme- B, perforin, LFA-1, and CD94-CD159a heterodimer (1). Within the ILC family, the re...
The NK cell population is characterized by distinct NK cell subsets that respond differently to t... more The NK cell population is characterized by distinct NK cell subsets that respond differently to the various activating stimuli. For this reason, the determination of the optimal cytotoxic activation of the different NK cell subsets can be a crucial aspect to be exploited to counter cancer cells in oncologic patients. To evaluate how the triggering of different combination of activating receptors can affect the cytotoxic responses of different NK cell subsets, we developed a microbead-based degranulation assay. By using this new assay, we were able to detect CD107a+ degranulating NK cells even within the less cytotoxic subsets (i.e., resting CD56bright and unlicensed CD56dim NK cells), thus demonstrating its high sensitivity. Interestingly, signals delivered by the co-engagement of NKp46 with 2B4, but not with CD2 or DNAM-1, strongly cooperate to enhance degranulation on both licensed and unlicensed CD56dim NK cells. Of note, 2B4 is known to bind CD48 hematopoietic antigen, therefore...
Although NK cells are considered part of the innate immune system, a series of evidences has demo... more Although NK cells are considered part of the innate immune system, a series of evidences has demonstrated that they possess characteristics typical of the adaptive immune system. These NK adaptive features, in particular their memory-like functions, are discussed from an ontogenetic and evolutionary point of view.
Background. Human Natural killer (NK) cells are characterized by NK cell receptors (NKRs) with in... more Background. Human Natural killer (NK) cells are characterized by NK cell receptors (NKRs) with inhibitory and activatory function that finely control their functional activities. In particular, they express inhibitory receptors for MHC class I molecules, named killer cell immunoglobulin (Ig)-like receptors (KIRs) and C-type lectin CD94-CD159a, and many triggering molecules like NKp30, NKp44, NKp46,(called natural cytotoxicity receptors, NCRs), NKG2D, CD161, and CD244. The majority of peripheral blood human NK cells are ...
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Papers by Flavia Buccella