Homeostasis of naive and memory CD4+ T cells: IL-2 and IL-7 differentially regulate the balance between proliferation and Fas-mediated apoptosis

Jaleco, S.; Swainson, L.; Dardalhon, V.; Burjanadze, M.; Kinet, S.; Taylor, N.

J Immunol

2003-07-01 / vol 171 / pages 61-8


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.

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Humans; Cells, Cultured; Adult; Apoptosis/*immunology; Cell Movement/immunology; Enzyme Activation/immunology; Trans-Activators/metabolism; DNA-Binding Proteins/metabolism; Signal Transduction/immunology; *Immunologic Memory; Cell Division/immunology; Interleukin-2/*physiology; Receptors, Interleukin-7/physiology; *Milk Proteins; Antigens, CD95/biosynthesis/*physiology; Caspases/metabolism; CD4-Positive T-Lymphocytes/*cytology/immunology/metabolism; Cell Differentiation/immunology; Fetal Blood; Homeostasis/*immunology; Interleukin Receptor Common gamma Subunit; Interleukin-7/*physiology; Interphase/immunology; STAT5 Transcription Factor; T-Lymphocyte Subsets/*cytology/immunology/metabolism; Thymus Gland/cytology/immunology

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