Enhanced HIV replication in monocytic cells following engagement of adhesion molecules and contact with stimulated T cells.
HIV-infected macrophages form a major reservoir of virus within tissue and are present in multiple tissue sites. Control of HIV replication within this cell population is likely to have profound effects on the pathogenesis of HIV infection. Cell-cell interaction between CD4+ T cells and macrophages is a crucial part of antigen presentation and has the potential to continually seed HIV infection of such T cells, maintaining high levels of infected cells within lymph nodes. Interaction of T cells and macrophages is controlled by engagement of cell membrane adhesion molecules which effect discrete intracellular signalling pathways. We have investigated the effects of cross-linkage of specific adhesion molecules and contact with T cells on HIV replication in chronically infected monocytic cell line OM10.1. Cross-linkage of CD18, CD29 or CD45 by immobilized antibodies specifically enhanced HIV replication in OM10.1 cells; cross-linkage of a panel of other cell surface proteins had no effect on HIV replication. Enhancement of HIV replication following cross-linkage of CD18, CD29 or CD45 was dependent upon TNF alpha secretion. Such adhesion molecules are involved in macrophage adhesion to other cells. In further experiments, we demonstrated that contact of OM10.1 cells with stimulated fixed T cells or isolated T-cell membranes potently enhanced HIV replication in a TNF-dependent manner, while in contrast, unstimulated fixed T cells or T-cell membranes had no effect on HIV replication. Cross-linkage of monocyte cell membrane adhesion molecules on contact with stimulated fixed T cells mimics adhesion molecule ligation induced during antigen presentation. Activation of HIV replication in monocytic cells on T cell-macrophage adhesion during antigen presentation would facilitate HIV infection and subsequent deletion of CD4+ T cells in an antigen-specific manner. This phenomenon may play a role in the sequential loss of antigen specific CD4+ T cells seen in HIV-infected patients.
Division of Infectious Diseases, St George's Hospital Medical School, Tooting, London.
R J
RJ
Shattock
D
D
Burger
J M
JM
Dayer
G E
GE
Griffin
D017951:Antigen Presentation; D000936:Antigen-Antibody Complex / Q000502:physiology; D018821:CD18 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000276:immunology; D002460:Cell Line; D018920:Coculture Techniques; D006678:HIV / Q000254:growth & development* / Q000472:pathogenicity; D006801:Humans; D019012:Integrin beta1 / Q000276:immunology; D007375:Interleukin-1 / Q000276:immunology; D017493:Leukocyte Common Antigens / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000821:virology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000936:Antigen-Antibody Complex; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D019012:Integrin beta1; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D017493:Leukocyte Common Antigens