title: CD8+ T-cell-derived soluble factor(s), but not beta-chemokines RANTES, MIP-1 alpha, and MIP-1 beta, suppress HIV-1 replication in monocyte/macrophages.
abstract: It has been demonstrated that CD8+ T cells produce a soluble factor(s) that suppresses human immuno-deficiency virus (HIV) replication in CD4+ T cells. The role of soluble factors in the suppression of HIV replication in monocyte/macrophages (M/M) has not been fully delineated. To investigate whether a CD8+ T-cell-derived soluble factor(s) can also suppress HIV infection in the M/M system, primary macrophages were infected with the macrophage tropic HIV-1 strain Ba-L. CD8+ T-cell-depleted peripheral blood mononuclear cells were also infected with HIV-1 IIIB or Ba-L. HIV expression from the chronically infected macrophage cell line U1 was also determined in the presence of CD8+ T-cell supernatants or beta-chemokines. We demonstrate that: (i) CD8+ T-cell supernatants did, but beta-chemokines did not, suppress HIV replication in the M/M system; (ii) antibodies to regulated on activation normal T-cell expressed and Secreted (RANTES), macrophage inflammatory protein 1 alpha (MIP-1 alpha) and MIP-1 beta did not, whereas antibodies to interleukin 10, interleukin 13, interferon alpha, or interferon gamma modestly reduced anti-HIV activity of the CD8+ T-cell supernatants; and (iii) the CD8+ T-cell supernatants did, but beta-chemokines did not, suppress HIV-1 IIIB replication in peripheral blood mononuclear cells as well as HIV expression in U1 cells. These results suggest that HIV-suppressor activity of CD8+ T cells is a multifactorial phenomenon, and that RANTES, MIP-1 alpha, and MIP-1 beta do not account for the entire scope of CD8+ T-cell-derived HIV-suppressor factors.
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: H
authors.initials: H
authors.lastname: Moriuchi
authors.forename: M
authors.initials: M
authors.lastname: Moriuchi
authors.forename: C
authors.initials: C
authors.lastname: Combadiere
authors.forename: P M
authors.initials: PM
authors.lastname: Murphy
authors.forename: A S
authors.initials: AS
authors.lastname: Fauci
mesh_terms: D000818:Animals; D016645:Aotidae; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000502:physiology*; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000494:pharmacology*; D018920:Coculture Techniques; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation; D019402:Macrophage Inflammatory Proteins / Q000494:pharmacology*; D008264:Macrophages / Q000821:virology*; D009000:Monocytes / Q000821:virology*; D011994:Recombinant Proteins / Q000494:pharmacology; D014020:Tissue Extracts; D014779:Virus Replication / Q000187:drug effects* / Q000502:physiology
chemical_list: D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D007376:Interleukin-2; D019402:Macrophage Inflammatory Proteins; D011994:Recombinant Proteins; D014020:Tissue Extracts