Publication Abstract Display
Type: Published Manuscript
Title: Mechanisms of immune activation of Human Immunodeficiency Virus in monocytes/macrophages.
Authors: Schrier RD, McCutchan JA, Wiley CA
Contact: Department of Pathology, University of California, San Diego, La Jolla 92093.
Year: 1993
Publication: Journal of Virology
Volume: 67 Issue: 10 Pages: 5713-20
Abstract:Monocytes/macrophages (M/M) are the major host of human immunodeficiency virus (HIV) in solid tissues. However, blood monocytes are nonpermissive for HIV infection, indicating that M/M activation or differentiation is necessary for HIV replication. Since M/M are activated during immune responses, we investigated the effect of T-cell activation on HIV expression in M/M derived from peripheral blood of HIV-infected individuals. Previously, we reported that coculture of monocytes from HIV-infected donors with T cells andmitogens resulted in M/M differentiation and HIV expression. Production of HIV by M/M from infected donors required direct contact between monocytes and T cells (for the first 24 h), and the response to alloantigens, but not mitogens, was restricted to HLA-DR. In this study, we found that HIV was more readily recovered from M/M of asymptomatic HIV seropositive donors (69%) than from M/M of symptomatic donors (57%). Viral antigens (e.g., inactivated herpes simplex virus) could initiate the immune response and HIV expression. The ability of noninfected T cells to activate HIV expression in M/M and observations that treatments of M/M with antibodies to deplete T cells did not reduce HIV expression suggested that the monocytes were endogenously infected. To define the aspects of immune activation specifically involved in initiating HIV expression in M/M, interactions of M/M and T cells and participation of cytokines were investigated. The T cell which activated M/M was CD4+ CD8-. Fixed allogeneic cells are known to induce T-cell activation but were not able to serve as antigen for M/M differentiation, suggesting that M/M may need to function as antigen-presenting cells to receive the signal to differentiate and express HIV. Blocking of M/M-T-cell interaction with antibodies directed against LFA-1 or interleukin-1 prevented HIV expression. However, inhibition of later stages of T-cell activation, such as blocking of interleukin-2 receptors, did not diminish HIV expression in M/M. Consistent with the requirement for cell-cell contact between M/M and T cells, a variety of cytokines were unable to initiate HIV replication in M/M. The ability of T cells to induce cellular differentiation and HIV replication in M/M in vitro suggests that initiation of an immune response to an antigen, such as an opportunistic pathogen, could be a mechanism by which HIV disseminates to tissues in vivo.
Funding: CSAP:SP MIMH SP50 MH 45294, NIMH:MH R01 MH46790
Keywords: Antigens, CD, Antigens, CD3, Antigens, CD4, Cell Differentiation, Cells, Cultured, HIV, HIV Core Protein p24, HIV Infections, Humans, Lymphocyte Activation, Macrophages, Monocytes, Reference Values, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S., T-Lymphocyte Subsets, T-Lymphocytes

return to publications listing