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Human immunodeficiency virus type 1 infection of antigen-specific CD4 cytotoxic T lymphocytes
P A Robbins1, G L Roderiquez, K W Peden
1Laboratory of Cell and Viral Regulation, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892, USA.
Insights
Antigen presentation helps CD4 T cells fight M-tropic HIV-1 by releasing chemokines, but not T-tropic HIV-1. This suggests CD4 T cells may offer early protection against certain HIV-1 strains.
Area of Science:
- Immunology
- Virology
Background:
- Human immunodeficiency virus type 1 (HIV-1) infects various immune cells.
- CD4 cytotoxic T lymphocytes (CTLs) play a role in viral immunity.
Purpose of the Study:
- To investigate how M-tropic and T-tropic HIV-1 strains affect antigen-specific CD4 CTLs.
- To determine the role of antigen presentation in HIV-1 infection of CD4 CTLs.
Main Methods:
- Utilized a CD4 CTL line specific for an influenza B virus hemagglutinin peptide.
- Infected CD4 CTLs with M-tropic (HIV-1AD) and T-tropic (HIV-1LAI) HIV-1 strains.
- Assessed cytotoxicity, chemokine production, and CCR5 expression with and without antigen presentation.
Main Results:
- Both HIV-1 strains productively infected CD4 CTLs, reducing cytotoxicity.
- Antigen presentation increased CC chemokine secretion (RANTES, MIP-1beta), suppressed M-tropic HIV-1 replication, and preserved CTL recognition.
- Antigen presentation did not protect against T-tropic HIV-1 infection or preserve CTL recognition.
Conclusions:
- CD4 CTLs can harbor or suppress M-tropic HIV-1 depending on antigen presence.
- CD4 CTLs lack suppressors for T-tropic HIV-1LAI.
- CD4 CTLs may offer early protection against M-tropic HIV-1 during initial infection stages.
Abstract:
The effect of macrophage (M)-tropic and T cell line (T)-tropic human immunodeficiency virus type 1 (HIV-1) infection on antigen-specific CD4 cytotoxic T lymphocytes (CTLs) has been studied using a CD4 CTL line specific for a peptide from influenza B virus hemagglutinin. In the absence of antigen presentation, the production of CC chemokines was low. Both the M-tropic HIV-1 strain (HIV-1AD) and the T-tropic HIV-1 strain (HIV-1LAI) established productive infections in the CD4 CTLs, decreasing antigen-specific cytotoxicity. Peptide presented to the CD4 CTLs increased their secretion of RANTES and MIP-1beta, suppressed M-tropic HIV-1 replication, downmodulated CCR5 expression, and preserved CTL recognition. The suppression of M-tropic HIV-1 replication and downmodulation of the CCR5 receptor likely resulted from CC chemokine secretion since antibodies to CC chemokines restored M-tropic HIV-1 replication. Antigen presentation did not protect CD4 CTLs from T-tropic HIV-1 infection or preserve their CTL recognition. Thus, these CD4 CTLs do not make suppressor factors that inhibit the T-tropic HIV-1LAI isolate. The results indicate that these CD4 CTLs can either harbor or suppress M-tropic HIV-1 infection, depending on whether antigen is present. CD4 CTLs might therefore provide some protection in the early stages of HIV-1 infection when M-tropic isolates are present.