INDUCTION OF CD4(-CELL DEPLETION IN MICE DOUBLY TRANSGENIC FOR HIV GP120 AND HUMAN CD4() T)

It has been suggested that loss of uninfected T cells in HIV infection occurs because of lymphocyte activation resulting in cell death by ap optosis. To address the question of whether cross-linking of CD4/HIV g p120 complexes by antibodies were sufficient to induce T cell depletio n in vivo, we developed an animal model of continuous interaction betw een human CD4 (hCD4), gp120 and anti-gp120 antibodies in the absence o f other viral factors. Double-transgenic mice have been generated in w hich T cells express on their membrane hCD4 and secrete HIV gp120. Alt hough these mice have hCD4/gp120 complexes present on the surface of T cells, they do not show gross immunological abnormalities, and they a re able to produce anti-gp120 antibodies following immunization with d enaturated gp120. However, double-transgenic mice with antibodies to g p120, when immunized with tetanus toroid, mount an IgG response that i s significantly lower than that of double-transgenic mice without anti bodies to gp120. Furthermore, the presence of anti-gp120 antibodies le ads to CD4(+) T cell depletion and immunodeficiency in the absence of HIV infection. Thus, the antibody response to gp120 can lead to CD4(+) T cell attrition in vivo.