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.
Department of Medicine, Laboratory for AIDS Virus Research, New York Hospital-Cornell Medical Center, New York 10021.
J
J
Laurence
J
J
Kulkosky
B
B
Dong
E
E
Early
R
R
Snyderman
G J
GJ
Cianciolo
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