HIV-infected humans, but not chimpanzees, have circulating cytotoxic T lymphocytes that lyse uninfected CD4+ cells.
It has been suggested that autoimmune phenomena contribute to the depletion of CD4+ T cells and the development of AIDS in HIV-1 infected humans based, in part, on observations that some HIV-1-infected humans have autoantibodies reactive with Ag expressed on uninfected CD4+ cells. In this study, 11 of 14 asymptomatic HIV-1-infected homosexuals and hemophiliacs, but none of 17 uninfected homosexuals or heterosexuals, were found to have cytotoxic lymphocytes in blood that can lyse uninfected CD4+ T cells from humans and chimpanzees but not human B lymphoblastoid cells or mouse T cells. The cytotoxic PBL were concluded to be CTL rather than NK cells, with the phenotype being CD3+, TCR-1 alpha beta+, CD8+, CD4-, CD16- based on findings that PBL-mediated lysis of uninfected CD4+ cells was 1) blocked by a mAb to CD3, which inhibits CTL but not NK activity; 2) diminished by treatment of PBL with a mAb to CD8 and C, but not by treatment with mAb to CD4 or CD16 and C; and 3) blocked by mAb WT31 directed against the TCR-1 alpha beta. In contrast, PBL from HIV-1-infected chimpanzees, which to date have not developed AIDS, lacked detectable CTL lytic for uninfected CD4+ cells.
Zarling
J M
JM
Oncogen, Seattle, WA 98121.
Ledbetter
J A
JA
Sias
J
J
Fultz
P
P
Eichberg
J
J
Gjerset
G
G
Moran
P A
PA
D000818:Animals; D000943:Antigens, Differentiation / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000382:microbiology; D003602:Cytotoxicity, Immunologic; D015658:HIV Infections / Q000276:immunology*; D007111:Immunity, Cellular; D007158:Immunologic Techniques; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1; D051379:Mice; D002679:Pan troglodytes / Q000276:immunology* / Q000382:microbiology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D016028:Receptors, Leukocyte-Adhesion / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000943:Antigens, Differentiation; D016169:Lymphocyte Function-Associated Antigen-1; D011948:Receptors, Antigen, T-Cell; D016028:Receptors, Leukocyte-Adhesion