title: Human immunodeficiency virus type 1 infection of antigen-specific CD4 cytotoxic T lymphocytes.
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.
authors.affiliation: Laboratory of Cell and Viral Regulation, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892, USA.
authors.forename: P A
authors.initials: PA
authors.lastname: Robbins
authors.forename: G L
authors.initials: GL
authors.lastname: Roderiquez
authors.forename: K W
authors.initials: KW
authors.lastname: Peden
authors.forename: M A
authors.initials: MA
authors.lastname: Norcross
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D002460:Cell Line; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000378:metabolism; D015536:Down-Regulation; D015497:HIV-1 / Q000276:immunology / Q000502:physiology*; D006801:Humans; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism; D019713:Receptors, CCR5 / Q000096:biosynthesis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism / Q000821:virology*
chemical_list: D054407:Chemokine CCL4; D018946:Chemokine CCL5; D019402:Macrophage Inflammatory Proteins; D019713:Receptors, CCR5