Kinetics of immune functions and virus replication during HIV-1 infection.
BACKGROUND
Kinetics of human immunodeficiency virus type 1 (HIV-1) cytotoxic T lymphocyte (CTL) responses and viral load were evaluated in HIV-1 infected homosexual men who progressed to AIDS within 3-6 years after seroconversion and in long-term survivors who remained AIDS-free for > 9 years with normal CD4+ T cell counts.


METHODS
CTL against four major HIV-1 gene products (i.e. Gag, reverse transcriptase (RT), Nef and Env) were expanded in vitro under limiting dilution conditions using antigen specific stimulation. CTL activity was measured in standard split-well 51Cr-release assay. Viral load was measured both as serum HIV-1 RNA levels and frequency of circulating CD4+ T cells productively infected with HIV-1. Polyclonal T cell function in vitro was determined in whole blood lymphocyte cultures, measuring lymphoproliferative responses to CD3 monoclonal antibody.


RESULTS
Long-term survival was associated with either persistently high or stable low HIV-1 specific CTL responses, accompanied by preserved in vitro polyclonal T cell reactivity and low viral load. In progressors, HIV-1 specific CTL responses were initially generated with similar kinetics as compared to long-term survivors. However, with progression to AIDS antiviral CTL activity and T cell function deteriorated simultaneously, while viral load increased.


CONCLUSIONS
Our results are consistent with the hypothesis that HIV-1 specific CTL are beneficial through control of viremia to the virologic set-point and contribute to maintenance of the asymptomatic phase. However, loss of HIV-1 specific immune control as part of a more general loss of T cell function is the precipitating event in AIDS pathogenesis.
Pontesilli
O
O
Department Clinical Viro-Immunology, Central Laboratory of The Netherlands Red Cross Blood Transfusion Service, University of Amsterdam, The Netherlands. clbkvi@xs4all.nl
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 / Q000276:immunology / Q000821:virology; D018450:Disease Progression; D015658:HIV Infections / Q000276:immunology* / Q000821:virology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D008297:Male; D017741:Survivors; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D019562:Viral Load; D014779:Virus Replication