Kinetics of Gag-specific cytotoxic T lymphocyte responses during the clinical course of HIV-1 infection: A longitudinal analysis of rapid progressors and long-term asymptomatics.
To gain more insight into the role of HIV-1-specific cytotoxic T lymphocytes (CTL) in the pathogenesis of AIDS, we investigated temporal relations between HIV-1 Gag-specific precursor CTL (CTLp), HIV-1 viral load, CD4+ T cell counts, and T cell function. Six HIV-1-infected subjects, who were asymptomatic for more than 8 yr with CD4+ counts > 500 cells/mm3, were compared with six subjects who progressed to AIDS within 5 yr after HIV-1 seroconversion. In the long-term asymptomatics, persistent HIV-1 Gag-specific CTL responses and very low numbers of HIV-1-infected CD4+ T cells coincided with normal and stable CD4+ counts and preserved CD3 mAb-induced T cell reactivity for more than 8 yr. In five out of six rapid progressors Gag-specific CTLp were also detected. However, early in infection the number of circulating HIV-1-infected CD4+ T cells increased despite strong and mounting Gag-specific CTL responses. During subsequent clinical progression to AIDS, loss of Gag-specific CTLp coincided with precipitating CD4+ counts and severe deterioration of T cell function. The possible relationships of HIV-1 Gag-specific CTLp to disease progression are discussed.
|Keywords||0 (Gene Products, gag), Acquired Immunodeficiency Syndrome/immunology, Adult, CD4 Lymphocyte Count, Comparative Study, Cytotoxicity, Immunologic, Disease Progression, Gene Products, gag/*immunology, HIV Infections/*immunology/virology, HIV-1/*immunology/isolation & purification, Human, Kinetics, Longitudinal Studies, Support, Non-U.S. Gov't, T-Lymphocytes, Cytotoxic/*immunology, Viremia/immunology|
Klein, M.R., van Baalen, C.A., Holwerda, A.M., Kerkhof Garde, S.R., Bende, R.J., Keet, I.P.M., … Miedema, F.. (1995). Kinetics of Gag-specific cytotoxic T lymphocyte responses during the clinical course of HIV-1 infection: A longitudinal analysis of rapid progressors and long-term asymptomatics.. The Journal of Experimental Medicine, 181, 1365–1372. Retrieved from http://hdl.handle.net/1765/3534