Background: Despite immunodeficiency of CD4+ T cells, HIV+ kidney and liver transplant patients experience higher rejection rates compared to HIV- patients. Most of the rejection occurs shortly after transplantation suggesting that the enhanced rejection may be due to generalized immune activation or preformed memory responses to donor-alloantigens.

Methods: We analyzed banked peripheral blood samples collected from HIV+ patients collected just before transplant. We used multicolor flow cytometry to compare the activation status of T cells between rejectors and non-rejectors. We developed a modified mixed lymphocyte reaction to determine the frequency of donor-alloantigen reactive CD8+ T cells, conventional CD4+ T cells, and Tregs. We also determined the frequency of preformed IFNg-producing anti-donor memory T cells. In addition, we developed a novel approach to measure T cell cross-reactivity between donor-alloantigen and HIV antigens. We challenged short-term donor-alloantigen reactive T cell lines and polyclonal T cell lines with pooled peptides from a panel of HIV, HCV, CMV, and EBV antigens. We measured T cell reactivity by monitoring proliferation and expression of CD98 using flow cytometry.

Results: Using multicolor flow cytometry, we did not detect differences in the effector/memory T phenotype in rejectors compared to non-rejectors. However, we found preliminary evidence of an altered balance between donor-reactive CD8+ T cells and Tregs and increased donor stimulated IFNg production by CD45RA- CD8+ T cells in rejectors. To determine whether the increased frequency of donor-reactive memory CD8+ T cells is due to cross-reactivity between HIV-specific T cells and donor-alloantigen reactive T cells, we measured the cross-reactivity between donor and HIV-antigens. In one kidney rejector, 21.4% of the donor-reactive CD8+ T cells cross-reacted with HIV antigens. The polyclonal line from the same patient had 46.1% of the CD8+ T cells react to HIV antigens, suggesting that a robust anti-HIV response may have primed donor-reactive memory T cells in this patient.

Conclusion: These findings suggest that preformed memory T cell reactivity to donor-alloantigen distinguishes rejectors from non-rejectors and that cross-reactivity between donor-alloantigen and HIV antigen may explain the heightened rejection in some HIV+ patients.

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