COSTIMULATORY PROPERTIES OF THE HUMAN CD4 MOLECULE - ENHANCEMENT OF CD3-INDUCED T-CELL ACTIVATION BY HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 THROUGH VIRAL ENVELOPE GLYCOPROTEIN GP120
T. Oravecz et Ma. Norcross, COSTIMULATORY PROPERTIES OF THE HUMAN CD4 MOLECULE - ENHANCEMENT OF CD3-INDUCED T-CELL ACTIVATION BY HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 THROUGH VIRAL ENVELOPE GLYCOPROTEIN GP120, AIDS research and human retroviruses, 9(10), 1993, pp. 945-955
This study was designed to investigate the T cell-costimulatory activi
ty of ligands binding to different regions on the human CD4 molecule.
We assayed the costimulatory properties of a panel of CD4 MAbs, intact
HIV, and viral envelope glycoproteins in CD3-induced activation of re
sting T cell subpopulations. Our data using MAbs reveal epitope-specif
ic variations in the functional activities of CD4 MAbs under specific
conditions in which CD3 and CD4 molecules are co-cross-linked. We show
that both naive and memory CD4+ T cell subsets are susceptible to CD4
-mediated costimulation, which overcomes the functional differences be
tween the two cell populations in responsiveness to CD3 MAbs. We show
for the first time that, analogous to CD4 MAbs, preparations of HIV an
d viral envelope glycoprotein gp120 are also potent costimulators of T
cell proliferation and IL-2 production. On the basis of these results
we propose possible mechanisms for polyclonal cell activation in the
course of HIV infection and suggest that viral inhibitory and costimul
atory effects may together disrupt the normal balanced function of the
immune system, leading to AIDS.