Anti-HIV type 1 cytotoxic T lymphocyte effector activity and disease progression in the first 8 years of HIV type 1 infection of homosexual men.
Cytotoxic T lymphocytes (CTL) may play an important role in host defense against HIV-1 infection. In this study, we examined the responses of circulating effector CTL (CTLe) specific for Gag, Pol, Env, and Tat in 57 HIV-1-infected men, 49 of whom were asymptomatic and had documented time since seroconversion of < 8 years. CTLe responses to at least one of the four HIV-1 gene products were detected in 83% of the subjects. The magnitude and prevalence of the anti-Tat responses were significantly less than the responses to Gag, Pol, and Env. Cell depletion studies indicated that the lytic activity against the HIV-1 structural proteins was mediated by CD8+ T cells, although 30% of Env-specific lysis was mediated by CD16+ natural killer cells. Anti-HIV-1 CTLe responses against Gag and Pol were significantly less in subjects infected for over 6 years as compared to those infected for shorter periods of time. We found no correlation, however, between anti-HIV-1 CTLe responses and either CD4+ or CD8+ T cell counts, rates of CD4+ T cell loss, HIV-1 infectious viral load, use of antiviral medications, or subsequent progression to AIDS. Our results indicate that anti-HIV-1 CTLe activity is relatively stable in asymptomatic subjects infected < 6 years, and is not an early marker for risk of disease progression.
Rinaldo
C R
CR
Department of Pathology, University of Pittsburgh School of Medicine, Pennsylvania 15261, USA.
Beltz
L A
LA
Huang
X L
XL
Gupta
P
P
Fan
Z
Z
Torpey
D J
DJ
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D015686:Gene Products, env / Q000276:immunology; D015683:Gene Products, gag / Q000276:immunology; D015684:Gene Products, pol / Q000276:immunology; D015696:Gene Products, tat / Q000276:immunology; D015658:HIV Infections / Q000097:blood / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology* / Q000302:isolation & purification; D018451:Homosexuality, Male; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D013997:Time Factors; D054322:tat Gene Products, Human Immunodeficiency Virus
D015686:Gene Products, env; D015683:Gene Products, gag; D015684:Gene Products, pol; D015696:Gene Products, tat; D054322:tat Gene Products, Human Immunodeficiency Virus