Cross-linking of CD45 on suppressive/regulatory T cells leads to the abrogation of their suppressive activity in vitro

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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 also 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. Here we report two newly established mAbs, which 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.