Regulation of IL-21 signaling by suppressor of cytokine signaling-1 (SOCS1) in CD8+ T lymphocytes

被引:44
作者
Gagnon, Julien [1 ]
Ramanathan, Sheela [1 ]
Leblanc, Chantal [1 ]
Ilangumaran, Subburaj [1 ]
机构
[1] Univ Sherbrooke, Fac Med, Dept Pediat, Div Immunol, Sherbrooke, PQ J1H 5N4, Canada
基金
加拿大健康研究院; 加拿大创新基金会;
关键词
SOCS1; cytokine; IL-21; IL-15; STAT3; STAT5; T lymphocyte; homeostasis; CD8 T cells;
D O I
10.1016/j.cellsig.2006.10.003
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Mice lacking the gene for suppressor of cytokine signaling I (SOCS 1) show defective homeostasis of T lymphocytes due to accumulation of CD8(+) T cells, resulting at least partly from dysregulated IL- 15 signaling. IL- 15 alone does not stimulate proliferation of naive CD8 T cells, but can synergize with IL-21 to induce proliferation, suggesting a potential role for IL-21 in the defective homeostasis of CD8(+) T lymphocytes in SOCS1(-/-) mice. Since IL-21 strongly induced SOCS I mRNA in CD8(+) T cells, we investigated whether SOCS I regulates their response to IL-21. CD8(+) T cells isolated from SOCS I deficient mice proliferated vigorously in response to IL-21 + IL-15. In CD8(+) T lymphocytes expressing transgenic TCR, IL-21 + IL-7 provided a stronger stimulus to naive cells whereas IL-15 + IL-21 potently stimulated memory cells. Compared to truly naive or memory cells, SOCS1(-/-) H-Y TC+ CD8(+) T cells displayed CD44(lo)Ly6C(hi)CD122(int)CD127(lo) partial memory phenotype and exhibited stronger response to IL-15 + IL-21 than truly naive cells. In SOCS1(-/-) CD8(+) T cells, IL-21 caused greater reduction in IL-15 threshold for activation in a dose-dependent manner. SOCS1 deficiency did not modulate IL-21R alpha expression or sensitivity to IL-21, but delayed the loss of IL-21-induced phospho-STAT3 signal. These results show that SOCS I is a critical regulator of IL-21 signaling in CD8+ T cells, and support the notion that sustained IL-21 signaling might also contribute to the aberrant T cell homeostasis in SOCS1-deficient mice. (c) 2006 Elsevier Inc. All rights reserved.
引用
收藏
页码:806 / 816
页数:11
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