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* Section of Immunology, Department of Mechanism of Aging, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, Aichi, Japan;
Division of Gene Function in Animals, Graduate School of Biological Sciences, Nara Institute of Science and Technology, Nara, Japan;
Department of Experimental Pathology, Institute for Frontier Medical Science, Kyoto University, Kyoto, Japan; and
Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Kawaguchi, Japan
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.
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