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.