gamma(c) cytokines provide multiple homeostatic signals to naive CD4(+) T cells.
Cytokines signaling through receptors sharing the common gamma chain (gamma(c)), including IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21, are critical for the generation and peripheral homeostasis of B, T and NK cells. To identify unique or redundant roles for gamma(c) cytokines in naive CD4(+) T cells, we compared monoclonal populations of CD4(+) T cells from TCR-Tg mice that were gamma(c) (+), gamma(c) (-), CD127(-/-) or CD122(-/-). We found that gamma(c) (-) naive CD4(+) T cells failed to accumulate in the peripheral lymphoid organs and the few remaining cells were characterized by small size, decreased expression of MHC class I and enhanced apoptosis. By over-expressing human Bcl-2, peripheral naive CD4(+) T cells that lack gamma(c) could be rescued. Bcl-2(+) gamma(c) (-) CD4(+) T cells demonstrated enhanced survival characteristics in vivo and in vitro, and could proliferate normally in vitro in response to antigen. Nevertheless, Bcl-2(+) gamma(c) (-) CD4(+) T cells remained small in size, and this phenotype was not corrected by enforced expression of an activated protein kinase B. We conclude that gamma(c) cytokines (primarily but not exclusively IL-7) provide Bcl-2-dependent as well as Bcl-2-independent signals to maintain the phenotype and homeostasis of the peripheral naive CD4(+) T cell pool.
Cytokines and Lymphoid Development Unit, Immunology Department, Institut Pasteur, Paris, France.
Guillemette X
GX
Masse
Erwan
E
Corcuff
Hélène
H
Decaluwe
Ursula
U
Bommhardt
Olivier
O
Lantz
Jan
J
Buer
James P
JP
Di Santo
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D049109:Cell Proliferation; D048429:Cell Size; D016207:Cytokines / Q000276:immunology* / Q000378:metabolism*; D004789:Enzyme Activation; D005786:Gene Expression Regulation; D006706:Homeostasis / Q000276:immunology*; D007113:Immunity, Innate / Q000276:immunology*; D053646:Interleukin-2 Receptor beta Subunit / Q000378:metabolism; D053699:Interleukin-7 Receptor alpha Subunit / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010641:Phenotype; D051057:Proto-Oncogene Proteins c-akt; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*
D016207:Cytokines; D053646:Interleukin-2 Receptor beta Subunit; D053699:Interleukin-7 Receptor alpha Subunit; D019253:Proto-Oncogene Proteins c-bcl-2; D051057:Proto-Oncogene Proteins c-akt