RESUMO
Lymphopenia-induced proliferation (LIP) is a proliferative program initiated in response to T cell insufficiency caused by acute or chronic immunodepletion. Studies of lymphopenic mice have demonstrated that the cytokine IL-7 and TCR signaling are critical for LIP. We examined how these two factors impact T cell proliferation following transfer into moderately lymphopenic mice. In this study, we show that moderate lymphopenia (â¼25% of wild-type lymphocytes) of IL-7Rα knock-in mutant (IL-7Rα(449F)) mice supports T cell proliferation, although with decreased frequency and kinetics compared with cells transferred to severely lymphopenic (5% of wild-type lymphocytes) IL-7Rα(-/-) hosts. Although previous studies have demonstrated that elevated IL-7 levels play an important role in LIP, IL-7 availability was not elevated in IL-7Rα(449F) mice. However, moderate lymphopenia increased access of transferred T cells to self-peptide presented on APCs that can trigger TCR signaling and proliferation. Importantly, we did not detect significant changes in TCR Vß usage of proliferated T cells recovered from either moderately or severely lymphopenic hosts. Our work demonstrates that polyclonal T cells retain a diverse TCR repertoire following proliferation mediated by either self-peptide-MHC interaction alone or in combination with IL-7, and that T cell reconstitution is most efficient in the presence of increased IL-7 availability.
Assuntos
Proliferação de Células , Interleucina-7/biossíntese , Linfopenia/imunologia , Linfopenia/patologia , Linfócitos T/imunologia , Linfócitos T/patologia , Regulação para Cima/imunologia , Animais , Disponibilidade Biológica , Doença Crônica , Citocinas/metabolismo , Técnicas de Introdução de Genes , Humanos , Interleucina-7/metabolismo , Interleucina-7/fisiologia , Depleção Linfocítica , Linfopenia/genética , Complexo Principal de Histocompatibilidade/genética , Complexo Principal de Histocompatibilidade/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Ligação Proteica/genética , Ligação Proteica/imunologia , Receptores de Interleucina-7/biossíntese , Receptores de Interleucina-7/deficiência , Receptores de Interleucina-7/genética , Baço/imunologia , Baço/metabolismo , Baço/patologia , Linfócitos T/metabolismo , Regulação para Cima/genéticaRESUMO
T cells rely on a duality of TCR and gammac cytokine signals for development, activation and peripheral T cell homeostasis. Previous data had suggested that the requirements for CD4 and CD8 memory T cell regulation were qualitatively distinct, but emerging data has shown that the requirements for true antigen specific memory T cells are very similar between these two cell types. This review will focus on contributions made by members of the gammac cytokine family (IL-2, IL-4, IL-7, IL-15 and IL-21) to homeostasis of naïve, memory phenotype and antigen experienced memory T cells.