CD4+CD25+Foxp3+ T cells and CD4+CD25-Foxp3+ T cells in aged mice.
Aging is associated with a progressive decline in T cell-mediated immune responses. However, it has been unknown whether regulatory/suppressive CD4 T cells are involved in this decline. Our in vitro analyses revealed that CD4+CD25+ T cells, the well-characterized naturally occurring regulatory/suppressive CD4 T cells, in aged mice are functionally comparable to those in young mice (i.e., anergic and suppressive), although slightly increased in number. In contrast, functional changes to whole CD4+CD25- T cells were pronounced in aged mice, i.e., the majority of aged CD4+CD25- T cells exhibited a significant hyporesponsiveness, and the remaining cells maintained a normal responsiveness. Furthermore, we identified Foxp3 (a transcription factor critical in conferring the regulatory/suppressive function to CD4 T cells)-positive suppressive CD4 T cells among aged hyporesponsive CD4+CD25- T cells. These results suggest that the age-related decline in T cell-mediated immune responses is ascribable to changes in the CD4+CD25- T cell population and not to a functional augmentation of suppressive CD4+CD25+ T cells.
Nishioka
Tomohisa
T
Section of Immunology, Department of Mechanism of Aging, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, Aichi, Japan.
Shimizu
Jun
J
Iida
Ryuji
R
Yamazaki
Sayuri
S
Sakaguchi
Shimon
S
D000375:Aging / Q000276:immunology*; D000818:Animals; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D017635:Clonal Anergy / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000096:biosynthesis*; D008213:Lymphocyte Activation; D008297:Male; D008546:Melanoma, Experimental; D051379:Mice; D008810:Mice, Inbred C57BL; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis* / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000378:metabolism
D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D015375:Receptors, Interleukin-2