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Treatment-Dependent Loss of Polyfunctional Cd8+ T-Cell Responses in HIV-Infected Kidney Transplant Recipients Is Associated with Herpesvirus Reactivation


Journal Article

Gasser, O.; Bihl, F.; Sanghavi, S.; Rinaldo, C.; Rowe, D.; Hess, C.; Stablein, D.; Roland, M.; Stock, P.; Brander, C.

Am J Transplant




Acyclovir; Adult; Aged; Antiviral Agents; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cell Survival; Cytomegalovirus; Flow cytometry; Ganciclovir; HIV Infections; HLA-A Antigens; HLA-B Antigens; HLA-DR Antigens

Antiretroviral-therapy has dramatically changed the course of HIV infection and HIV-infected (HIV(+)) individuals are becoming more frequently eligible for solid-organ transplantation. However, only scarce data are available on how immunosuppressive (IS) strategies relate to transplantation outcome and immune function. We determined the impact of transplantation and immune-depleting treatment on CD4+ T-cell counts, HIV-, EBV-, and Cytomegalovirus (CMV)-viral loads and virus-specific T-cell immunity in a 1-year prospective cohort of 27 HIV(+) kidney transplant recipients. While the results show an increasing breadth and magnitude of the herpesvirus-specific cytotoxic T-cell (CTL) response over-time, they also revealed a significant depletion of polyfunctional virus-specific CTL in individuals receiving thymoglobulin as a lymphocyte-depleting treatment. The disappearance of polyfunctional CTL was accompanied by virologic EBV-reactivation events, directly linking the absence of specific polyfunctional CTL to viral reactivation. The data provide first insights into the immune-reserve in HIV+ infected transplant recipients and highlight new immunological effects of thymoglobulin treatment. Long-term studies will be needed to assess the clinical risk associated with thymoglobulin treatment, in particular with regards to EBV-associated lymphoproliferative diseases.

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