title: Monocytes in HIV type 1-infected individuals lose expression of costimulatory B7 molecules and acquire cytotoxic activity.
abstract: Monocytes/macrophages control the function of lymphocytes through positive and negative regulation. They release immunostimulatory cytokines and initiate costimulatory signals in T cells through the expression of B7 molecules. Their negative regulatory functions include the capacity to destroy cells with which they form cellular conjugates. We show here that HIV-1 infection skews monocyte function toward negative regulation by restraining the expression of costimulatory B7 molecules and by enhancing the cytolytic monocyte function. Monocytes that express constitutively B7, a membrane component that facilitates the engagement of costimulatory signals in T cells, lose this marker after HIV-1 infection and become refractory to inducers of B7 expression. The appearance of monocytes with reduced B7 expression is associated with an increased cytolytic monocyte capacity. Monocytes from HIV-1-infected donors destroy antibody-targeted normal lymphocytes more efficiently than do normal monocytes and they destroy CD4+ T cells specifically without the exposure to an exogenous ligand. CD4-reactive HIV-1 envelope molecules, expressed on monocytes as a consequence of infection or of opsonization by antibody, may specifically target CD4+ T lymphocytes for destruction and may thereby contribute to the preferential loss of CD4 T cells in HIV-1-infected individuals.
authors.affiliation: Department of Microbiology and Immunology, New York Medical College, Valhalla 10595, USA.
authors.forename: A
authors.initials: A
authors.lastname: Dudhane
authors.forename: B
authors.initials: B
authors.lastname: Conti
authors.forename: T
authors.initials: T
authors.lastname: Orlikowsky
authors.forename: Z Q
authors.initials: ZQ
authors.lastname: Wang
authors.forename: N
authors.initials: N
authors.lastname: Mangla
authors.forename: A
authors.initials: A
authors.lastname: Gupta
authors.forename: G P
authors.initials: GP
authors.lastname: Wormser
authors.forename: M K
authors.initials: MK
authors.lastname: Hoffmann
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology*; D000328:Adult; D018122:B7-1 Antigen / Q000096:biosynthesis / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D002648:Child; D003602:Cytotoxicity, Immunologic; D015497:HIV-1; D006801:Humans; D009000:Monocytes / Q000276:immunology*
chemical_list: D018122:B7-1 Antigen