CD4 modulation of noninfected human T lymphocytes by HIV-1 envelope glycoprotein gp120: contribution to the immunosuppression seen in HIV-1 infection by induction of CD4 and CD3 unresponsiveness.
HIV-1 envelope glycoprotein (gp120) may contribute to the magnitude of the immunological defects observed in the early stages of HIV-1 infection by modulating CD4 from the cell surface and altering the function of both CD4 and CD3 in uninfected cells. We investigated CD4 expression as well as CD3- and CD4-mediated cell migration in normal peripheral blood T lymphocytes exposed to recombinant gp120 in long-term cultures for < or = 6 days. Single low doses of gp120 (0.5 microgram/ml) modulated CD4 by 4-6 h, reached a nadir at 24-72 h, and began to recover at 96 h. By day 6, surface expression of CD4 had rebounded to control levels. CD3 expression was unchanged at all time points. Concomitant with loss of surface CD4 was significant lessening of both anti-CD4 and anti-CD3 antibody-induced migration. Reexpression of CD4 at 96 h resulted in the recovery of both CD4- and CD3-mediated migration. Cycloheximide inhibited CD4 reexpression and both anti-CD4 and anti-CD3 antibody-induced migration in cells treated with gp120. These data suggest that CD4 modulation by gp120 results in loss of function, which persists until new membrane CD4 is generated. Persistent exposure of CD4+ cells to gp120 in vivo may contribute to the disproportionately large immunological deficits seen in the early stages of HIV-1 infection, in which most CD4+ cells remain uninfected.
Theodore
A C
AC
Pulmonary Center, Boston University School of Medicine, Massachusetts 02118.
Kornfeld
H
H
Wallace
R P
RP
Cruikshank
W W
WW
D017252:CD3 Complex / Q000276:immunology*; D015704:CD4 Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000382:microbiology; D002464:Cell Migration Inhibition; D002469:Cell Separation; D003513:Cycloheximide / Q000494:pharmacology; D005434:Flow Cytometry; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D007121:Immunocompetence; D007700:Kinetics; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology
D017252:CD3 Complex; D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D003513:Cycloheximide