CD4+CD25- T cells in aged mice are hyporesponsive and exhibit suppressive activity.
Studies on humans and rodents have established that functional deterioration of CD4 T cells occurs with aging. We report in this study that approximately 70% of CD4(+)CD25(-) T cell preparations from individual 24-mo-old mice are hyporesponsive to in vitro stimulation with anti-CD3 Ab. The remaining 30% of CD4(+)CD25(-) T cell preparations showing the intermediate or normal responsiveness in the primary stimulation also exhibit the hyporesponsive properties after primary stimulation. Both of these hyporesponsive aged CD4(+)CD25(-) T cells could inhibit the proliferation of cocultured CD4(+)CD25(-) T cells from young mice, like CD4(+)CD25(+) T cells, which have recently been demonstrated as an immune regulator in young mice. Another experiment revealed that hyporesponsive aged CD4(+)CD25(-) T cells arrest the cell division of cocultured young CD4(+)CD25(-) T cells. The suppressive activity observed in aged CD4(+)CD25(-) T cells is aging-dependent, not mediated by humoral factors, cell-contact dependent, and broken by the addition of IL-2 or anti-GITR Ab, but not by anti-CTLA-4 Ab. These studies show that aging not only leads to a decline in the ability to mount CD4(+)CD25(-) T cell responses, but at the same time, also renders these aged CD4(+)CD25(-) T cells suppressive.
Shimizu
Jun
J
Immunological Aging Research Group, Division of Physiology and Aging, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakae-cho, Itabashi-ku, Tokyo 173-0015, Japan. jun@tmig.or.jp
Moriizumi
Eiko
E
D000375:Aging / Q000276:immunology; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000276:immunology; D007108:Immune Tolerance; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D050378:T-Lymphocytes, Regulatory / Q000145:classification / Q000276:immunology* / Q000502:physiology
D015375:Receptors, Interleukin-2