Anti‐CD45RB and donor‐specific spleen cells transfusion inhibition allograft skin rejection mediated by memory T cells. Issue 2 (4th October 2016) - Jian, You‐Qiang
Abstract : Donor‐reactive memory T (Tm)cells mediate accelerated rejection, which is known as a barrier to the survival of transplanted organs. Selective interference with the anti‐CD45RB monoclonal antibody (α‐CD45RB) reliably induces donor‐specific tolerance. In this study, pre‐sensitization to female C57BL/6 mice with the skin of female BLAB/c mice generated a large number of Tm cells and resulted in rapid rejection of the secondly transplanted allografts. α‐CD45RB did induce the tolerance to skin allograft primarily transplanted but failed to induce tolerance in the pre‐sensitized mice. Donor‐specific spleen cell transfusion (DST) alone also failed to induce the tolerance in the pre‐sensitized recipients. Interestingly, combination of α‐CD45RB with DST inhibited the rejection induced by memory T cells in the pre‐sensitized mice. CD25+ T‐cell depletion in α‐CD45RB combined with DST therapy recipients could prevent skin allograft tolerance from establishing. In addition, adoptive transfer of donor‐primed memory T cells into the tolerant recipients markedly broke the established tolerance. Our findings indicate that α‐CD45RB and DST can synergistically inhibit the accelerated rejection mediated by memory T cells and induce long‐term skin allograft acceptance in mice.