The cell surface marker phenotype of macrophages from HIV-1-infected subjects reflects an IL-10-Enriched and IFN-gamma-deprived donor environment.
T cells depend on costimulation by accessory cells for an immune response. Costimulatory macrophage activity involves the expression of B7 molecules whose expression is upregulated by interferon-gamma (IFN-gamma) and downregulated by interleukin-10 (IL-10). The expression of low-affinity Fc gamma IIIR (CD16), in contrast, is upregulated in the presence of IL-10 and downregulated in the presence of IFN-gamma. In human immunodeficiency virus-1 (HIV-1) infection, the balance between IFN-gamma and IL-10 expression shifts toward IL-10 predominance. Herein, we compare B7 and CD16 macrophage phenotypes from healthy and from HIV-1-infected patients. Patient macrophages express B7 molecules in lower density than macrophages from healthy donors and are resistant to the upregulation of costimulatory molecule expression. B7 expression can be normalized in patient macrophages by treating them with anti IL-10 monoclonal antibodies (mAb) and IFN-gamma together but not by treatment with either anti-IL-10 mAb or IFN-gamma alone. This finding suggests an excess of IL-10 in HIV-1 infection and an IFN-gamma deficiency, consistent with previous cytokine assessments in HIV-1-infected subjects. The upregulation of CD16 expression was readily induced in patient macrophages by treatment with IL-10 and was inhibited by treatment with IFN-gamma. CD16 expression identifies the subset of cytotoxic macrophages that has been shown to destroy CD4T cells, which they target through CD4-reactive immune-complexed HIV-1 envelope molecules.
Orlikowsky
T
T
Department of Microbiology and Immunology, New York Medical College, Valhalla 10595, USA.
Wang
Z Q
ZQ
Dudhane
A
A
Horowitz
H
H
Conti
B
B
Hoffmann
M
M
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology*; D000937:Antigen-Antibody Reactions; D000954:Antigens, Surface / Q000097:blood*; D015415:Biomarkers; D015704:CD4 Antigens / Q000276:immunology; D002478:Cells, Cultured; D015536:Down-Regulation; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D008264:Macrophages / Q000276:immunology*; D010641:Phenotype; D013601:T-Lymphocytes / Q000276:immunology; D015854:Up-Regulation
D000954:Antigens, Surface; D015415:Biomarkers; D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D016753:Interleukin-10; D007371:Interferon-gamma