High-level HIV-1 viremia suppresses viral antigen-specific CD4(+) T cell proliferation.
In chronic viral infections of humans and experimental animals, virus-specific CD4(+) T cell function is believed to be critical for induction and maintenance of host immunity that mediates effective restriction of viral replication. Because in vitro proliferation of HIV-specific memory CD4(+) T cells is only rarely demonstrable in HIV-infected individuals, it is presumed that HIV-specific CD4(+) T cells are killed upon encountering the virus, and maintenance of CD4(+) T cell responses in some patients causes the restriction of virus replication. In this study, proliferative responses were absent in patients with poorly restricted virus replication although HIV-specific CD4(+) T cells capable of producing IFN-gamma were detected. In a separate cohort, interruption of antiretroviral therapy resulted in the rapid and complete abrogation of virus-specific proliferation although HIV-1-specific CD4(+) T cells were present. HIV-specific proliferation returned when therapy was resumed and virus replication was controlled. Further, HIV-specific CD4(+) T cells of viremic patients could be induced to proliferate in response to HIV antigens when costimulation was provided by anti-CD28 antibody in vitro. Thus, HIV-1-specific CD4(+) T cells persist but remain poorly responsive (produce IFN-gamma but do not proliferate) in viremic patients. Unrestricted virus replication causes diminished proliferation of virus-specific CD4(+) T cells. Suppression of proliferation of HIV-specific CD4(+) T cells in the context of high levels of antigen may be a mechanism by which HIV or other persistently replicating viruses limit the precursor frequency of virus-specific CD4(+) T cells and disrupt the development of effective virus-specific immune responses.
McNeil
A C
AC
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Shupert
W L
WL
Iyasere
C A
CA
Hallahan
C W
CW
Mican
J A
JA
Davey
R T
RT
Connors
M
M
D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D002455:Cell Division; D015488:HIV Antigens / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000254:growth & development* / Q000502:physiology; D006801:Humans; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D014766:Viremia / Q000276:immunology* / Q000821:virology; D014779:Virus Replication / Q000276:immunology*
D015488:HIV Antigens