AEGiS-11IAC: Kinetics of HIV-1 specific CTL during the clinical course of HIV-1 infection: further evidence for a general collapse of cellular immunity.

11th International AIDS Conference

Vancouver, British Columbia — July 7-12, 1996

Kinetics of HIV-1 specific CTL during the clinical course of HIV-1 infection: further evidence for a general collapse of cellular immunity.

Int Conf AIDS 1996 Jul 7-12; 11:223 (abstract no. Tu.A.281)
Klein MR, Pontesilli O, Holwerda AM, Kerkhof-Garde SR, de Wolf F, Miedema F; Dept. of Clin. Viro-Immunology, Central Lab. Netherlands Red Cross Blood Transfusion Service and Lab. For Exp. and Clin. Immunol. of the University of Amsterdam, Amsterdam, the Netherlands. Fax: +31 20 512 3310. E-mail: a306clbl@horus.sara.nl.

OBJECTIVE: Previously we reported on kinetics of Gag-specific cytotoxic T lymphocyte (CTL) (Klein et al. 1995, J.Exp.Med. 181:1365). Here we extend our findings by longitudinal studies on Gag-, Nef-, RT- and Env-specific responses and viral load in long-term survivors and in rapid progressors to AIDS.

METHODS: HIV-1 specific CTL were expanded in vitro using autologous B-LCL infected with recombinant vaccinia viruses expressing single HIV-1 derived genes. Standard techniques for limiting dilution and split-well 51Chromiumrelease assays were used to determine CTL precursor frequencies. HIV-1 cellular and RNA load was determined using clonal isolation procedures and quantitative NASBA respectively. Study population: Long-term survivors were HIV-1 seropositive homosexual men who remained AIDS-free for more than 8 years with greater than 400 CD4+ T cell microliter-1 (n=6). Control subjects were participants from the Amsterdam Cohort studies on AIDS who developed AIDS within 3-6 years after HIV-1 seroconversion (n=6).

RESULTS: Persistent HIV-1 specific CTL responses and low viral load were observed in long-term survivors suggestive for efficient viral control and maintenance of the asymptomatic state by CTL. In progressors also potent and broadly directed HIV-1 specific CTL responses were observed during the asymptomatic phase. However, viral load increased and in general HIV-1 specific CTL disappeared during progression to AIDS.

CONCLUSIONS: Kinetics of HIV-1 specific CTL against 4 major proteins during the course of HIV-1 were strikingly similar. Progression to AIDS occurs despite the presence of broadly directed and vigorous CTL responses during the asymptomatic phase. So, apparently HIV-1 specific CTL are no guarantee for protection to disease progression, but may be involved in maintaining the asymptomatic state in long-term survivors.

Keywords: AEGIS, HIV-1, HIV Infections, Acquired Immunodeficiency Syndrome, Viral Load, Immunity, Cellular, T-Lymphocytes, Cytotoxic, Disease Progression, HIV-1 Reverse Transcriptase, Homosexuality, Shock, Kinetics, Longitudinal Studies, Cohort Studies, Human, Male, In Vitro, immunology, ICA11

960707
TuA281