Kidney Rejection in HIV-Positive Recipients Is Associated With Immune Activation and Higher Frequency of Donor-Reactive CD8 Cells.

Abstract

Background: HIV+ kidney transplant recipients have 3 times higher rejection rate when compared to HIV- recipients. Approximately half of those who have at least one rejection experienced a rejection episode within the first 30 days after transplant, suggesting that the enhanced rejection may be due to potent immune activation or preformed memory responses to donor alloantigens. Methods: We analyzed banked peripheral blood samples from HIV+ patients collected just before transplant and compared to HIV+ disease status-matched non-transplant and HIV- age-matched control subjects. We compared the total CD4+ cell counts in the blood and used multicolor flow cytometry to determine the frequency of effector and memory T cells. The frequencies of donor-alloantigen-reactive CD8+ T cells, conventional CD4+ T cells, and regulatory T cells were measured using an improved one-way mixed lymphocyte reaction assay. Results: CD4+ T cell counts in HIV+ pre-transplant patients were not significantly lower than HIV- pre-transplant patients, likely because of the preferential enrollment of healthiest HIV+ patients defined by the study entry eligibility criteria. HIV+ transplant patients had higher percentages of CD4+CD45RA-CCR7- effector cells when compared with age-matched HIV+ non-transplant and HIV- patients (27.2±2.3, 12.0±2.0, vs. 16.1±3.0; n=52, 10, 9; p=0.0023). However, no difference between rejector and non-rejector was noted. HIV+ rejectors had higher frequency of donor-reactive CD8+ T cells when compared to non-rejectors (4.46±0.79 vs. 2.26±0.58; n=8, 8; p=0.045); whereas frequencies of CD4+ conventional T cells and regulatory T cells were not significantly different between the rejectors and the non-rejectors. Conclusion: Our results thus far are consistent with the interpretation that HIV+ transplant recipients have more activated immune system. Higher frequency of donor-reactive CD8+ T cell pre-transplant may distinguish rejectors from non-rejectors.