title: Treatment-dependent loss of polyfunctional CD8+ T-cell responses in HIV-infected kidney transplant recipients is associated with herpesvirus reactivation.
abstract: 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.
authors.affiliation: Partners AIDS Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA. ogasser@partners.org
authors.forename: O
authors.initials: O
authors.lastname: Gasser
authors.forename: F
authors.initials: F
authors.lastname: Bihl
authors.forename: S
authors.initials: S
authors.lastname: Sanghavi
authors.forename: C
authors.initials: C
authors.lastname: Rinaldo
authors.forename: D
authors.initials: D
authors.lastname: Rowe
authors.forename: C
authors.initials: C
authors.lastname: Hess
authors.forename: D
authors.initials: D
authors.lastname: Stablein
authors.forename: M
authors.initials: M
authors.lastname: Roland
authors.forename: P
authors.initials: P
authors.lastname: Stock
authors.forename: C
authors.initials: C
authors.lastname: Brander
mesh_terms: D000212:Acyclovir / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002470:Cell Survival; D003587:Cytomegalovirus / Q000235:genetics; D005434:Flow Cytometry; D015774:Ganciclovir / Q000627:therapeutic use; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy; D015234:HLA-A Antigens / Q000276:immunology; D015235:HLA-B Antigens / Q000276:immunology; D006684:HLA-DR Antigens / Q000276:immunology; D006564:Herpesviridae / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D004854:Herpesvirus 4, Human / Q000187:drug effects / Q000235:genetics; D006801:Humans; D016030:Kidney Transplantation / Q000276:immunology* / Q000473:pathology; D008875:Middle Aged; D018579:Patient Selection; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000473:pathology; D019562:Viral Load; D014775:Virus Activation / Q000276:immunology / Q000502:physiology*
chemical_list: D000998:Antiviral Agents; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D006684:HLA-DR Antigens; D015774:Ganciclovir; D000212:Acyclovir