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Keywords:

  • Alloantibodies;
  • clinical outcome;
  • donor-reactive DTH;
  • kidney;
  • simultaneous kidney-pancreas;
  • transplantation

Evidence of transplant recipient cellular sensitization towards donor antigens has rarely been directly measured. Rather, sensitization has been generally inferred by the presence of detectable allo-reactive or donor-reactive antibodies. In this study a newly developed delayed-type hypersensitivity assay was used to directly determine the incidence of post-transplant donor-reactive T-cell sensitization in a large cohort of kidney and simultaneous kidney-pancreas recipients. These results were compared with the presence of detectable circulating alloantibodies and with patient clinical outcome. We found an unexpectedly high incidence (52%) of donor-reactive delayed-type hypersensitivity reactivity in our study patients. Donor-reactive delayed-type hypersensitivity reactivity occurred at a much higher frequency than detectable alloantibodies (20%). Further, we found no correlation between the presence of alloantibodies and donor-reactive delayed-type hypersensitivity reactivity. We also found no correlation between the development of donor-reactive delayed-type hypersensitivity reactivity and the degree of donor and recipient HLA matching. Finally, the presence of detectable donor-reactive delayed-type hypersensitivity reactivity did not correlate with a worse clinical outcome at the time of these analyses. We conclude that in transplant recipients, the presence of circulating alloantibodies is a poor indicator of previous T-cell sensitization to donor antigens. We also conclude that our current immunosuppression strategies are relatively ineffective at blocking T-cell allosensitization, but are very effective at blocking the biological consequences of that allosensitization.