Regulatory T cells are critical to tolerance induction in presensitized mouse transplant recipients through targeting memory T cells

American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons
W GeH Wang

Abstract

Memory T cells are a significant barrier to induction of transplant tolerance. However, reliable means to target alloreactive memory T cells have remained elusive. In this study, presensitization of BALB/c mice with C57BL/6 skin grafts generated a large number of OX40(+)CD44(hi)effector/memory T cells and resulted in rapid rejection of donor heart allografts. Recognizing that anti-OX40L monoclonal antibody (mAb) (alpha-OX40L) monotherapy prolonged graft survival through inhibition and apoptosis of memory T cells in presensitized recipients, alpha-OX40L was added to the combined treatment protocol of LF15-0195 (LF) and anti-CD45RB (alpha-CD45RB) mAb-a protocol that induced heart allograft tolerance in non-presensitized recipients but failed to induce tolerance in presensitized recipients. Interestingly, this triple therapy restored donor-specific heart allograft tolerance in our presensitized model that was associated with induction of tolerogenic dendritic cells and CD4(+)CD25(+)Foxp3(+) T regulatory cells (Tregs). Of note, CD25(+) T cell depletion in triple therapy recipients prevented establishment of allograft tolerance. In addition, adoptive transfer of donor-primed effector/memory T cells into tolerant recipients markedly ...Continue Reading

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Citations

Mar 1, 2012·Clinica Chimica Acta; International Journal of Clinical Chemistry·Stephan Schlickeiser, Birgit Sawitzki
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Mar 14, 2021·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Wee-Song Yeo, Qin Xiang Ng

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