Homeostasis of naive and memory CD4+ T cells: IL-2 and IL-7 differentially regulate the balance between proliferation and Fas-mediated apoptosis.
Cytokines play a crucial role in the maintenance of polyclonal naive and memory T cell populations. It has previously been shown that ex vivo, the IL-7 cytokine induces the proliferation of naive recent thymic emigrants (RTE) isolated from umbilical cord blood but not mature adult-derived naive and memory human CD4(+) T cells. We find that the combination of IL-2 and IL-7 strongly promotes the proliferation of RTE, whereas adult CD4(+) T cells remain relatively unresponsive. Immunological activity is controlled by a balance between proliferation and apoptotic cell death. However, the relative contributions of IL-2 and IL-7 in regulating these processes in the absence of MHC/peptide signals are not known. Following exposure to either IL-2 or IL-7 alone, RTE, as well as mature naive and memory CD4(+) T cells, are rendered only minimally sensitive to Fas-mediated cell death. However, in the presence of the two cytokines, Fas engagement results in a high level of caspase-dependent apoptosis in both RTE as well as naive adult CD4(+) T cells. In contrast, equivalently treated memory CD4(+) T cells are significantly less sensitive to Fas-induced cell death. The increased susceptibility of RTE and naive CD4(+) T cells to Fas-induced apoptosis correlates with a significantly higher IL-2/IL-7-induced Fas expression on these T cell subsets than on memory CD4(+) T cells. Thus, IL-2 and IL-7 regulate homeostasis by modulating the equilibrium between proliferation and apoptotic cell death in RTE and mature naive and memory T cell subsets.
Jaleco
Sara
S
Institut de Génétique Moléculaire de Montpellier, Centre National de la Recherche Scientifique Unité Mixte de Recherche 5535/Institut Fédératif de Recherche 122, Montpellier, France.
Swainson
Louise
L
Dardalhon
Valérie
V
Burjanadze
Maryam
M
Kinet
Sandrina
S
Taylor
Naomi
N
D000328:Adult; D017209:Apoptosis / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D004789:Enzyme Activation / Q000276:immunology; D005312:Fetal Blood; D006706:Homeostasis / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D053631:Interleukin Receptor Common gamma Subunit; D007376:Interleukin-2 / Q000502:physiology*; D015851:Interleukin-7 / Q000502:physiology*; D007399:Interphase / Q000276:immunology; D008894:Milk Proteins; D020395:Receptors, Interleukin-7 / Q000502:physiology; D050799:STAT5 Transcription Factor; D015398:Signal Transduction / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology; D015534:Trans-Activators / Q000378:metabolism; D019014:fas Receptor / Q000096:biosynthesis / Q000502:physiology*
D004268:DNA-Binding Proteins; C507941:IL2RG protein, human; D053631:Interleukin Receptor Common gamma Subunit; D007376:Interleukin-2; D015851:Interleukin-7; D008894:Milk Proteins; D020395:Receptors, Interleukin-7; D050799:STAT5 Transcription Factor; D015534:Trans-Activators; D019014:fas Receptor; D020169:Caspases