Aging-dependent generation of suppressive CD4+CD25-R123loCD103+ T cells in mice.
Advancing age is associated with significant alterations in immune functions, including a decline in CD4 T cell function, in both mice and humans. In our previous report, we showed that CD4(+)CD25(-) T cells in aged (24-month-old) mice, especially after in vitro pre-stimulation of these cells, exhibit hyporesponsive and suppressive properties. We examined here whether the suppressive activity of aged CD4(+)CD25(-) T cells is ascribable to a particular population within these cells. In vitro analyses revealed that cell populations rapidly extruding Rhodamine-123 (R123) (referred to as R123(lo) cells) in aged CD4(+)CD25(-) T cells have a more potent suppressive function compared with R123(hi) populations. In addition, CD103(+) cells in freshly prepared aged CD4(+)CD25(-)R123(lo) T cells had a most potent suppressive activity. Both R123(hi) and R123(lo) populations had individually stronger suppressive activity after pre-stimulation than before pre-stimulation. Furthermore, the R123(lo) population in young CD4(+)CD25(-) T cells also had different properties from R123(hi) T cells: low responsiveness, no additive effect in proliferation assays, and the gain of a suppressive function after in vitro pre-stimulation. Taken together, these results suggest that CD4(+)CD25(-)R123(lo) T cells are a unique population within whole CD4(+)CD25(-) T cells. This population exists in the early stage of the life span, and the properties in this population become obvious with aging, that is the gain of their suppressive activity.
Shimizu
Jun
J
Immunological Aging Research Group, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan. jun@tmig.or.jp
Moriizumi
Eiko
E
D000375:Aging / Q000276:immunology*; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D039001:Integrin alpha Chains / Q000378:metabolism*; D051379:Mice; D015375:Receptors, Interleukin-2 / Q000378:metabolism*; D020112:Rhodamine 123 / Q000378:metabolism*
D015703:Antigens, CD; D039001:Integrin alpha Chains; D015375:Receptors, Interleukin-2; C091367:alpha E integrins; D020112:Rhodamine 123