Human immunodeficiency virus type 1 envelope glycoprotein gp120 produces immune defects in CD4+ T lymphocytes by inhibiting interleukin 2 mRNA.
Envelope glycoprotein gp120 of human immunodeficiency virus type 1 (HIV-1) is known to inhibit T-cell function, but little is known about the mechanisms of this immunosuppression. Pretreatment of a CD4+ tetanus toxoid-specific T-cell clone with soluble gp120 was found to exert a dose-dependent inhibition of soluble antigen-driven or anti-CD3 monoclonal antibody-driven proliferative response, interleukin 2 (IL-2) production, and surface IL-2 receptor (IL-2R) alpha-chain expression, all of which were reversed by the addition of exogenous IL-2. mRNA for the gene encoding IL-2 was suppressed by treatment with gp120, but IL-2R gene transcription was not inhibited. Bypass activation of the T-cell clone with phorbol 12-myristate 13-acetate plus ionomycin was unaffected by gp120 pretreatment. Thus, gp120-CD4 interaction interferes with an essential role of the CD4 molecule in signal transduction through the CD3-antigen receptor (Ti) complex. Such a mechanism of gp120-induced immunosuppression, if operative in vivo, could contribute to the depressed specific immune responses associated with HIV infection.
Oyaizu
N
N
Department of Pediatrics, North Shore University Hospital-Cornell University Medical College, Manhasset, NY 11030.
Chirmule
N
N
Kalyanaraman
V S
VS
Hall
W W
WW
Pahwa
R
R
Shuster
M
M
Pahwa
S
S
D015703:Antigens, CD / Q000276:immunology; D015152:Blotting, Northern; D015704:CD4 Antigens / Q000276:immunology*; D002462:Cell Membrane / Q000276:immunology; D002478:Cells, Cultured; D002999:Clone Cells; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics*; D008213:Lymphocyte Activation; D012333:RNA, Messenger / Q000037:antagonists & inhibitors* / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology*
D015703:Antigens, CD; D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D007376:Interleukin-2; D012333:RNA, Messenger