Alloantibodies Prevent the Induction of Transplantation Tolerance by Enhancing Alloreactive T Cell Priming

  • Burns A
  • Chong A
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Abstract

Circulating alloantibodies in transplant recipients are often associated with increased Ab-mediated as well as cellular rejection. We tested the hypothesis that alloantibodies facilitate cellular rejection by functioning as opsonins to enhance T cell activation using a BALB/c to C57BL/6 heart or skin transplant model. Long-term heart and skin survival induced with anti-CD154 alone or in combination with donor-specific transfusion (DST), respectively, was abrogated by the presence of anti-Kd mAbs, and alloreactive T cell activation as well as acute rejection was observed. The prevention of graft acceptance in the skin model was dependent on anti-Kd binding to and converting DST from tolerigenic to immunogenic. Adoptive transfer of CFSE-labeled TCR-transgenic T cells into B6 recipients treated with anti-CD154/DST revealed the ability of anti-Kd to enhance the proliferation of anti–Kd-specific T cells via the indirect pathway as well as of non–Kd-reactive, recipient MHC-restricted CD4+ and CD8+ T cells. Thus, alloantibodies with restricted specificity are able to facilitate the indirect presentation as well as the cross-presentation of a larger repertoire of “linked” donor-derived Ags. These observations highlight the ability of alloantibodies to function not only in classical humoral rejection but also as opsonins that facilitate the CD40-CD154–independent activation of alloreactive T cells.

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Burns, A. M., & Chong, A. S. (2011). Alloantibodies Prevent the Induction of Transplantation Tolerance by Enhancing Alloreactive T Cell Priming. The Journal of Immunology, 186(1), 214–221. https://doi.org/10.4049/jimmunol.1001172

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