Gamma(c) deficiency precludes CD8+ T cell memory despite formation of potent T cell effectors.
Several cytokines (including IL-2, IL-7, IL-15, and IL-21) that signal through receptors sharing the common gamma chain (gamma(c)) are critical for the generation and peripheral homeostasis of naive and memory T cells. Recently, we demonstrated that effector functions fail to develop in CD4(+) T cells that differentiate in the absence of gamma(c). To assess the role of gamma(c) cytokines in cell-fate decisions that condition effector versus memory CD8(+) T cell generation, we compared the response of CD8(+) T cells from gamma(c)(+) or gamma(c)(-) P14 TCR transgenic mice after challenge with lymphocytic choriomeningitis virus. The intrinsic IL-7-dependent survival defect of gamma(c)(-) naive CD8(+) T cells was corrected by transgenic expression of human Bcl-2. We demonstrated that although gamma(c)-dependent signals are dispensable for the initial expansion and the acquisition of cytotoxic functions following antigenic stimulation, they condition the terminal proliferation and differentiation of CD8(+) effector T cells (i.e., KLRG1(high) CD127(low) short-lived effector T cells) via the transcription factor, T-bet. Moreover, the gamma(c)-dependent signals that are critical for memory T cell formation are not rescued by Bcl2 overexpression. Together, these data reveal an unexpected divergence in the requirement for gamma(c) cytokines in the differentiation of CD4(+) versus CD8(+) cytotoxic T lymphocytes.
Decaluwe
Hélène
H
Cytokines and Lymphocyte Development Unit, Institut Pasteur, Paris F-75015, France.
Taillardet
Morgan
M
Corcuff
Erwan
E
Munitic
Ivana
I
Law
Helen K W
HK
Rocha
Benedita
B
Rivière
Yves
Y
Di Santo
James P
JP
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007156:Immunologic Memory / Q000235:genetics / Q000276:immunology*; D053631:Interleukin Receptor Common gamma Subunit / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism
D053631:Interleukin Receptor Common gamma Subunit; D019253:Proto-Oncogene Proteins c-bcl-2