Monocytes in HIV type 1-infected individuals lose expression of costimulatory B7 molecules and acquire cytotoxic activity.
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.
Dudhane
A
A
Department of Microbiology and Immunology, New York Medical College, Valhalla 10595, USA.
Conti
B
B
Orlikowsky
T
T
Wang
Z Q
ZQ
Mangla
N
N
Gupta
A
A
Wormser
G P
GP
Hoffmann
M K
MK
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*
D018122:B7-1 Antigen