A soluble inhibitor of T lymphocyte function induced by HIV-1 infection of CD4+ T cells: characterization of a cellular protein and its relationship to p15E.
Soluble suppressor factor (SSF), first described in association with HIV-1 infection in vivo, is a molecule(s) capable of inhibiting T cell-dependent immune reactivity. Its relationship to human immunodeficiency virus (HIV) was further defined as supernatants of mononuclear cell cultures from HIV-1-seropositive carriers, CD4+ T lymphocytes infected with HIV-1 in vitro, and a T cell hybridoma incorporating CD4+ lymphocytes from an HIV-1-seropositive individual were shown to elaborate factors with similar activity profiles. These factors were recognized antigenically by certain antibodies directed against epitopes of p15E, a transmembrane protein of murine leukemia virus which shares regions of identity with proteins deduced from human endogenous retroviral envelope transcripts as well as HIV. These reagents precipitated a single-chain, nonglycosylated, nonviral protein of molecular weight 57,000 Da from SSF-producing cells. There was no cross-reactivity with antisera recognizing the IL-2R alpha-chain (CD25) or tumor necrosis factor. This molecule was present in very low levels in PHA-activated T lymphocytes and was upregulated following their infection with HIV-1. Isolation of HIV-linked SSF should permit comparisons with other virion, cellular, and serum inhibitory substances described in AIDS, and perhaps suggest therapeutic strategies.
Laurence
J
J
Department of Medicine, Laboratory for AIDS Virus Research, New York Hospital-Cornell Medical Center, New York 10021.
Kulkosky
J
J
Dong
B
B
Early
E
E
Snyderman
R
R
Cianciolo
G J
GJ
D000956:Antigens, Viral / Q000032:analysis*; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000382:microbiology* / Q000502:physiology; D003429:Cross Reactions; D015683:Gene Products, gag / Q000276:immunology* / Q000502:physiology; D015658:HIV Infections / Q000503:physiopathology*; D015497:HIV-1 / Q000254:growth & development; D006801:Humans; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D019590:Nucleocapsid Proteins; D011506:Proteins / Q000276:immunology*; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism; D012995:Solubility; D013491:Suppressor Factors, Immunologic / Q000276:immunology*; D014779:Virus Replication; D054301:gag Gene Products, Human Immunodeficiency Virus
D000956:Antigens, Viral; D015683:Gene Products, gag; D019590:Nucleocapsid Proteins; D011506:Proteins; D013491:Suppressor Factors, Immunologic; D054301:gag Gene Products, Human Immunodeficiency Virus; C060295:p15 gag protein, Human immunodeficiency virus 1; D012194:RNA-Directed DNA Polymerase