IL-2 differentially regulates perforin and FasL mediated cytotoxicity in CD4 T cells (33.10)
| Autor: | Deborah M. Brown, Leah Harris, Tyler Moore, Susan L. Swain, Shirley A. Condon |
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| Rok vydání: | 2009 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 182:33.10-33.10 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.182.supp.33.10 |
| Popis: | CD4 T cell effectors can promote survival against lethal influenza virus via perforin mediated cytolytic mechanisms, however; our understanding of how naïve CD4 cells differentiate into class II restricted killers remains obscure. To address this, TCR Tg CD4 cells were activated in vitro and examined for their ability to lyse target cells. We found that cytokine polarized CD4 T cell effectors displayed cytolytic activity with the hierarchy Th0>Th1>Th2>Th17; however, IL-6, TGF-β, IL-10, IL-12 or TNF-α were not required for inducing cytolytic activity in CD4 effectors. Antigen dose had a marked effect on cytotoxicity: low concentrations of peptide induced more potent cytolytic activity than relatively high concentrations. At low peptide concentration, exogenous IL-2 was necessary to drive granzyme B (GrB) expression and perforin mediated lysis. Using IL-2 deficient T cells, we found that IL-2 signaling was required in the first 24 h of culture, but increasing concentrations of IL-2 did not increase cytolytic activity. Studies are underway to determine whether Stat5 signaling is required for induction of cytolytic activity in CD4 T cells. Thus, low antigen dose and early activation signals via IL-2 direct the CD4 T cell response toward effectors with perforin mediated cytolytic potential. |
| Databáze: | OpenAIRE |
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