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* Department of Surgery and
Department of Medicine, Transplant Center, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215
Broad T cell depletion has been used as an integral part of treatment in transplantation and autoimmune diseases. Following depletion, residual T cells undergo homeostatic proliferation and convert to memory-like T cells. In this study, we investigated the effect of T cell depletion by antilymphocyte serum (ALS), a polyclonal anti-T cell Ab, on CD4+ regulatory T cells. After ALS treatment, CD4+CD25+ T cells underwent proliferation and expressed a memory T cell marker, CD44. One week after ALS treatment, both CD25+ and CD25– T cells exhibited increased suppression of alloresponses in vitro, which waned thereafter to the levels mediated by naive CD25+ and CD25– T cells. By real-time PCR analyses, ALS treatment of CD4-deficient mice adoptively transferred with Thy1.2+CD4+CD25+Foxp3+ and Thy1.1+CD4+CD25–Foxp3– T cells resulted in the appearance of Thy1.2+CD4+CD25–Foxp3+ and Thy1.1+CD4+CD25+Foxp3+ T cells, suggesting the conversion between CD25+ and CD25– T cells. Naive CD25+ T cells expressed a higher level of intracellular Bcl-xL than CD25– T cells. Up-regulation of the Bcl-xL molecule during ALS-induced homeostatic expansion further promoted survival of CD25+ and, to a lessor degree, CD25– cells. These results indicate that CD25+ T cells are spared from ALS-mediated deletion, with some CD25+ T cells converting to CD25– T cells, and continue to exhibit regulatory activity. The concomitant presence of T cell deletion and continuous regulatory T cell activity may underlie the therapeutic effect of ALS, particularly in treatment of autoimmune diseases.
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