Monocyte-mediated T cell suppression by HIV-2 envelope proteins.
HIV-2 is associated with an attenuated form of HIV disease. We investigate here the immunosuppressive effects of the HIV-2 envelope protein, gp105. We found that gp105 suppresses activation of T cells through a monocyte-mediated mechanism. Suppression of T cell activation by gp105 depends on contact between monocytes and T cells, but not on CD4+CD25+ T cells. The TLR4 pathway is likely involved, since gp105 activates TLR4 signaling and induces TNF-alpha production by monocytes. Immunosuppression is viewed as the main pathophysiologic consequence of infection by HIV. However, the main immunologic defect caused by HIV, depletion of T cells, requires T cell activation. Our findings are consistent with a new concept that HIV-2 envelope proteins act on monocytes to suppress T cell activation and that this property may contribute to the benign course of HIV-2. We hypothesize that the HIV-2 envelope immunosuppressive properties limit bursts of T cell activation, thus reducing viremia and contributing to the slow rate of disease progression that characterizes HIV-2 disease.
Cavaleiro
Rita
R
Unidade de Imunologia Clínica, Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.
Brunn
Gregory J
GJ
Albuquerque
Adriana S
AS
Victorino
Rui M M
RM
Platt
Jeffrey L
JL
Sousa
Ana E
AE
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D017252:CD3 Complex / Q000276:immunology; D002450:Cell Communication; D002478:Cells, Cultured / Q000276:immunology; D015498:HIV-2 / Q000276:immunology / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D008213:Lymphocyte Activation; D009000:Monocytes / Q000276:immunology*; D016328:NF-kappa B / Q000502:physiology; D015398:Signal Transduction / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000502:physiology; D014774:Virulence / Q000276:immunology; D054299:env Gene Products, Human Immunodeficiency Virus / Q000502:physiology*
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D016328:NF-kappa B; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D054299:env Gene Products, Human Immunodeficiency Virus; C069790:gp105 envelope protein, Human immunodeficiency virus 2