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CD4⁺CD25^- T Cells in Aged Mice Are Hyporesponsive and Exhibit Suppressive Activity ¹

Jun Shimizu^2,* and Eiko Moriizumi

^* Immunological Aging Research Group, Division of Physiology and Aging, and Molecular Gerontology Research Group, Division of Molecular Gerontology, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan

Studies on humans and rodents have established that functional deterioration of CD4 T cells occurs with aging. We report in this study that 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.

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