Anti‐CD45RB and donor‐specific spleen cells transfusion inhibition allograft skin rejection mediated by memory T cells

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.

The Entangled World of Memory T Cells and Implications in Transplantation

“…72 Treatment with anti-CD45RB and DST prevented memory TCMR in presensitized mice, suggesting it could be a potential target to inhibit early acute rejection. 73 Sphingosine-1-phosphate receptor 1 signaling is a key mediator of T-cell trafficking, which can be blocked by the sphingosine-1-phosphate receptor 1 antagonist FTY720. Of note, FTY720 combined with CTLA4-Ig or tacrolimus significantly increased graft survival, primarily by decreasing the frequency of T CM and T EM in the periphery and delaying overall T-cell recruitment into the graft in both presensitized mouse models and NHPs, which suggests it could function to regulate the alloreactive memory T-cell response even when administered only as a short-course therapy after transplantation.…”

Expression of viral CD45 ligand E3/49K on porcine cells reduces human anti-pig immune responses

“…Both the human cytomegalovirus (HCMV) glycoprotein pUL11 and human adenovirus type 64 (HAdV-D64 ; old taxonomy: Ad19a) protein E3/49K interact with the human cell surface protein tyrosine phosphatase CD45, which is essential for proper signaling via T and B cell antigen receptor associated pathways 21 – 23 . Binding of pUL11 and E3/49K or anti-CD45 antibodies is regarded to alter the phosphatase activity of CD45, thereby interfering with activating signaling pathways 24 – 30 . Inhibition of proliferation and cytokine production, enhanced production of immune attenuating cytokines (e.g.…”