AEGiS-15IAC: Functional differences in HIV-1-specific T cells induced by immunization versus natural infection.

15th International AIDS Conference

Bangkok, Thailand - July 11-16, 2004

Functional differences in HIV-1-specific T cells induced by immunization versus natural infection.

Int Conf AIDS 2004 Jul 11-16; 15:(abstract no. ThOrA1395)

Horton H
Fred Hutchinson Cancer Research Center, Seattle, United States

BACKGROUND: Antiviral CD8+ T cells exert a major role in controlling HIV1 infection and many preventive vaccine strategies are designed to elicit these cells. As chronic disease ensues, HIV1 specific T cells typically become functionally impaired, but it is not known if this is the case in those elicited by vaccination in uninfected persons. Hence, we characterized and compared the functional properties of T cells recognizing the Gag epitope, RLRPGGKKK (RK9), in HIV1 uninfected, immunocompetent candidate canarpox vaccine (vCP1452, Aventis) recipients and in HIV1 infected individuals.

METHODS: PBMCs obtained from HLA A3 positive vaccinees and HIV1 infected donors were tested for RK9 specific IFNgamma secretion. CD8+ T cells were tested for binding to HLA3 RK9 class I tetramers in contrast to a control tetramer using flow cytometry. Intracellular production of IFNgamma was contrasted with TNF-α and IL2. Proliferation to the RK9 peptide was examined by CFSE staining using flow cytometry.

RESULTS: We found IFNgamma secreting, HLA A3 restricted RK9 specific CD8+ T cells in 3 vaccinees and 10 infected individuals (4 LTNP, 6 with acute or chronic infection) with plasma viremia ranging from<50 to 57,795 copies/ml. The magnitudes of RK9 specific responses ranged from 0.08 to 3.42% CD8+ T cells by tetramer staining. When derived from vaccinees and acutely infected patients, the RK9 specific T cells proliferated and secreted IFNgamma, TNF-α and IL2. However, RK9 specific T cells from chronically infected individuals were not able to proliferate or secrete IL2 and were primed to apoptose when they reencountered peptide.

CONCLUSIONS: Preliminary evidence indicates that Gag RK9 specific T cells are fully functional when induced by vaccination but not when found in chronic infection. Thus, strategies that can arm the host with CD8+ T cells capable of secreting multiple antiviral CD8+ T cells upon initial exposure to HIV1 and maintain these responses despite acquisition of infection may lead to amelioration of disease sequelae.

Keywords: AEGIS, HIV-1, T-Lymphocytes, CD8-Positive T-Lymphocytes, Communicable Diseases, Interleukin-2, HLA-A3 Antigen, T-Lymphocytes, Cytotoxic, Viremia, CD4-Positive T-Lymphocytes, Vaccination, Flow Cytometry, Humans, immunology

040711
ThOrA1395