title: HIV envelope suppresses CD4+ T cell activation independent of T regulatory cells.
abstract: We previously demonstrated that HIV envelope glycoprotein (Env), delivered in the form of a vaccine and expressed by dendritic cells or 293T cells, could suppress Ag-stimulated CD4(+) T cell proliferation. The mechanism remains to be identified but is dependent on CD4 and independent of coreceptor binding. Recently, CD4(+) regulatory T (Treg) cells were found to inhibit protective anti-HIV CD4(+) and CD8(+) T cell responses. However, the role of Tregs in HIV remains highly controversial. HIV Env is a potent immune inhibitory molecule that interacts with host CD4(+) cells, including Treg cells. Using an in vitro model, we investigated whether Treg cells are involved in Env-induced suppression of CD4(+) T cell proliferation, and whether Env directly affects the functional activity of Treg cells. Our data shows that exposure of human CD4(+) T cells to Env neither induced a higher frequency nor a more activated phenotype of Treg cells. Depletion of CD25(+) Treg cells from PBMC did not overcome the Env-induced suppression of CD4(+) T cell proliferation, demonstrating that CD25(+)FoxP3(+) Treg cells are not involved in Env-induced suppression of CD4(+) T cell proliferation. In addition, we extend our observation that similar to Env expressed on cells, Env present on virions also suppresses CD4(+) T cell proliferation.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Haitao
authors.initials: H
authors.lastname: Hu
authors.forename: Kathy
authors.initials: K
authors.lastname: Fernando
authors.forename: Houping
authors.initials: H
authors.lastname: Ni
authors.forename: Drew
authors.initials: D
authors.lastname: Weissman
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D002460:Cell Line; D049109:Cell Proliferation; D002478:Cells, Cultured; D006678:HIV / Q000276:immunology; D019302:HIV Envelope Protein gp160 / Q000276:immunology / Q000378:metabolism*; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D008213:Lymphocyte Activation; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D019302:HIV Envelope Protein gp160; D016212:Transforming Growth Factor beta; D016753:Interleukin-10