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
Mr. Klein et al., 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(4), 1995, pp. 1365-1372
To gain more insight into the role of HIV-1-specific cytotoxic T lymph
ocytes (CTL) in the pathogenesis of AIDS, we investigated temporal rel
ations between HIV-1 Gag-specific precursor CTL. (CTLp), HIV-1 viral l
oad, CD4(+) T cell counts, and T cell function. Six HIV-1-infected sub
jects, who were asymptomatic for more than 8 yr with CD4(+) counts >50
0 cells/mm(3), 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-spec
ific CTL responses. During subsequent clinical progression to AIDS, lo
ss of Gag-specific CTLp coincided with precipitating CD4(+) counts and
severe deterioration of T cell function. The possible relationships o
f HIV-1 Gag-specific CTLp to disease progression are discussed.