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Cross-Linking of CD45 on Suppressive/Regulatory T Cells Leads to the Abrogation of Their Suppressive Activity In Vitro¹

Jun Shimizu^2,3,*, Ryuji Iida^2,*,¶, Yuji Sato, Eiko Moriizumi, Atsushi Nishikawa and Yasumasa Ishida^¶

^* Immunological Aging Research Group, Glycobiology Research Group, and Molecular Gerontology Research Group, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan; Department of Applied Biological Science, Tokyo University of Agriculture and Technology, Tokyo, Japan; and ^¶ Division of Gene Function in Animals, Graduate School of Biological Sciences, Nara Institute of Science and Technology, Nara, Japan

CD4⁺CD25⁺ T cells have immunoregulatory and suppressive functions and are responsible for suppressing self-reactive cells and maintaining self-tolerance. In addition to CD4⁺CD25⁺ T cells, there is some evidence that a fraction of CD4⁺CD25^– T cells exhibit suppressive activity in vitro or in vivo. We have shown, using aged mice, that aging not only leads to a decline in the ability to mount CD4⁺CD25^– T cell responses, but, at the same time, renders aged CD4⁺CD25^– T cells suppressive. In this study we report two newly established mAbs that could abrogate the suppressive function of aged CD4⁺CD25^– T cells. These mAbs recognized the same protein, the transmembrane phosphatase CD45. Cross-linking of CD45 on aged CD4⁺CD25^– T cells was required for the disruption of their suppressive activity. Surprisingly, these mAbs also abrogated the suppressive action of CD4⁺CD25⁺ T cells in vitro. Our results demonstrate an unexpected function of CD45 as a negative regulator neutralizing the suppressive activity of aged CD4⁺CD25^– and young CD4⁺CD25⁺ T cells.

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