Treatment-dependent loss of polyfunctional CD8+ T-cell responses in HIV-infected kidney transplant recipients is associated with herpesvirus reactivation.

Publication Type
Journal Article
Year of Publication
Gasser, O; Bihl, F; Sanghavi, S; Rinaldo, C; Rowe, D; Hess, C; Stablein, D; Roland, M; Stock, P; Brander, C
Am J Transplant
Date Published
2009 Apr
Acyclovir; Adult; Aged; Antiviral Agents; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cell Survival; Cytomegalovirus; Flow cytometry; Ganciclovir; Herpesviridae; Herpesvirus 4, Human; HIV Infections; HLA-A Antigens; HLA-B Antigens; HLA-DR Antigens; Humans; kidney transplantation; Middle Aged; Patient Selection; T-Lymphocytes, Cytotoxic; Viral Load; Virus Activation

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.