Crosslinking CD4 by human immunodeficiency virus gp120 primes T cells for activation-induced apoptosis.
These results provide an explanation for the enhancement of infection by certain antibodies against human immunodeficiency virus, and for the paradox that HIV appears to cause acquired immune deficiencysyndrome after the onset of antiviral immunity
From the "Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado 80206; the *Departments of Pediatrics and Biochemistry, Biophysics, and Genetics, University of ColoradoHealth Sciences Center, Denver, Colorado80262; the SLaboratoired'Immunologie, Institut de Recherches Cliniques de Montreal, Quebe~ H2W 1R7, Canada; IIBehringwerkeAG, D-3550 Marbur~ Germany; and 82 Cortx, Emeryville, California 94608
During human immunodeficiency virus infection there is a profound and selectivedecrease in the CD4 + population of T lymphocytes. The mechanism of this depletion is not understood, as only a small fraction of all CD4 + cells appear to be productively infected with HIV-1 in seropositive individuals
The data indicate that evenpicomolar concentrations of gp120 prime T cells for activationinduced cell death, suggesting a mechanism for CD4 + T cell depletion in acquired immune deficiencysyndrome, in the faceof concurrent infection and antigenic challenge with other organisms
Our data provide a mechanism for the recent observation that CD4 + T cells from HIV-infected individuals are primed in vivo for suicide by apoptosis, upon TCR activation by both superantigen and MHC class II-restricted antigens
Though this study does not address the question of apoptotic cell death in HIV-infected individuals, our observation that even picomolar concentrations of gp120 prime for activation-induced apoptosis suggests that this mechanism of cell death may be active in vivo
Our data provide a mechanism for the recent observation that CD4 § T cells from HIVoinfected asymptomatic individuals and acquired immune deficiencysyndrome patients are primed, in vivo, for suicide by apoptosis, upon T C R activation by both superantigen and M H C class II-restricted antigen