Interleukin 2, but not other common γ chain-binding cytokines, can reverse the defect in generation of CD4 effector T cells from naive T cells of aged mice

被引:195
作者
Haynes, L
Linton, PJ
Eaton, SM
Tonkonogy, SL
Swain, SL
机构
[1] Trudeau Inst Inc, Saranac Lake, NY 12983 USA
[2] Sidney Kidney Kimmel Canc Ctr, San Diego, CA 92121 USA
[3] N Carolina State Univ, Raleigh, NC 27606 USA
关键词
T cell receptor transgenic; CD4; cells; aging; IL-2; gamma c-binding cytokines;
D O I
10.1084/jem.190.7.1013
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Development of effecters from naive CD4 cells occurs in two stages. The early stage involves activation and limited proliferation in response to T cell receptor (TCR) stimulation by antigen and costimulatory antigen presenting cells, whereas the later stage involves proliferation and differentiation in response to growth factors. Using a TCR-transgenic (Tg(+)) model, we have examined the effect of aging on effector generation and studied the ability of gamma c signaling cytokines to reverse this effect. Our results indicate that responding naive CD4 cells from aged mice, compared with cells from young mice, make less interleukin (IL)-2, expand poorly between days 3 to 5, and give rise to fewer effecters with a less activated phenotype and reduced ability to produce cytokines. When exogenous IL-2 or other gamma c signaling cytokines are added during effector generation, the Tg(+) cells from both young and aged mice proliferate vigorously. However, IL-4, IL-7, and IL-15 all fail to restore efficient effector production. Only effecters from aged mice generated in the presence of IL-2 are able to produce IL-2 in amounts equivalent to those produced by effecters generated from young mice, suggesting that the effect of aging on IL-2 production is reversible only in the presence of exogenous IL-2.
引用
收藏
页码:1013 / 1023
页数:11
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