RESUMO
Signal 3 cytokines, such as IL-12 or type I IFN, support expansion and differentiation of CD8 T cells in vivo. If and how these two signal 3 cytokines compensate each other in T cell activation during different infections is so far unknown. Using CD8 T cells lacking receptors for IL-12, type I IFN or both, we show that the expansion of CD8 T cells depends on type I IFN (LCMV infection), type I IFN and IL-12 (Listeria and vesicular stomatitis virus infection) or is largely independent of the two cytokines (vaccinia virus infection). Furthermore, we show that CD8 T cells lacking IL-12 and type I IFN signals are impaired in cytokine production and cytolytic activity in the context of VSV and Listeria infection. These effector CD8 T cells fail to express KLRG1, thereby exhibiting a memory-like phenotype which correlated with lower expression of the transcription factor T-bet and higher expression of Eomes. This indicates that the variable interplay of both signal 3 cytokines is mandatory for cell fate decision of CD8 T cells in the context of different infections. Furthermore our results demonstrate that the pathogen-induced overall inflammatory milieu and not the antigen load and/or the quality of antigen presentation critically determine the signal 3 dependence of CD8 T cells.
Assuntos
Linfócitos T CD8-Positivos/imunologia , Imunidade/imunologia , Infecções/imunologia , Interferon Tipo I/imunologia , Interleucina-12/imunologia , Animais , Proliferação de Células , Infecções/microbiologia , Infecções/patologia , Infecções/virologia , Inflamação/imunologia , Inflamação/patologia , Listeriose/imunologia , Listeriose/patologia , Ativação Linfocitária/imunologia , Vírus da Coriomeningite Linfocítica/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Proteínas com Domínio T/metabolismo , Vesiculovirus/imunologiaRESUMO
Trogocytosis describes the transfer of surface determinants between immune cells and has been implicated in immune regulation. Most findings are based on in vitro studies since in vivo trogocytosis of immune cells is difficult to detect under physiological conditions. We used low frequencies of memory P14 T cells to demonstrate that T cells perform trogocytosis in vivo if in contact with APC pulsed with GP33-peptide or expressing the antigen endogenously. Furthermore, in vivo trogocytosis of T cells is demonstrated during infections with lymphocytic choriomeningitis virus and vaccinia virus. Trogocytosis-positive T cells revealed higher expression of activation marker and cytokines, showing a more activated phenotype compared to trogocytosis-negative T cells.