Longitudinal analysis of human immunodeficiency virus type 1-specific cytotoxic T lymphocyte responses: a predominant gag-specific response is associated with nonprogressive infection.
To establish correlates of protective immunity during human immunodeficiency virus type 1 (HIV-1) infection, the frequencies of circulating cytotoxic T lymphocyte (CTL) precursors (p) directed against 4 HIV-1 gene products (reverse transcriptase, gag, nef, and env) were evaluated in HIV-1-infected homosexual men who progressed to AIDS and in long-term survivors over time. For both groups, HIV-1-specific CTL responses had similar kinetics and magnitude. At maximum expansion, HIV-1-specific CTLp had a median frequency of 0.2% mononuclear cells in both progressors and long-term survivors, with peaks of 0.5% and 2%, respectively. Long-term survivors maintained the established CTLp pool and presented a persistently predominant gag-specific response. The fraction and, to a lesser extent, the frequency of gag-specific CTLp were inversely correlated with virus load. In progressors, general T cell function and measurable HIV-1-specific CTLp frequencies dropped simultaneously, suggesting a further loss of virus control due to the ensuing immunodeficiency.
Pontesilli
O
O
Department of Clinical Viro-Immunology, Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam, The Netherlands.
Klein
M R
MR
Kerkhof-Garde
S R
SR
Pakker
N G
NG
de Wolf
F
F
Schuitemaker
H
H
Miedema
F
F
D000163:Acquired Immunodeficiency Syndrome / Q000453:epidemiology / Q000276:immunology*; D018791:CD4 Lymphocyte Count; D018450:Disease Progression; D015686:Gene Products, env / Q000276:immunology; D015683:Gene Products, gag / Q000276:immunology*; D015693:Gene Products, nef / Q000276:immunology; D020276:HIV Long-Term Survivors; D054303:HIV Reverse Transcriptase / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006412:Hematopoietic Stem Cells / Q000276:immunology; D006716:Homosexuality; D006801:Humans; D008137:Longitudinal Studies; D008213:Lymphocyte Activation; D008297:Male; D009426:Netherlands / Q000453:epidemiology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D019562:Viral Load; D054311:nef Gene Products, Human Immunodeficiency Virus
D015686:Gene Products, env; D015683:Gene Products, gag; D015693:Gene Products, nef; D054311:nef Gene Products, Human Immunodeficiency Virus; D054303:HIV Reverse Transcriptase