An ongoing immune response to HIV envelope gp120 in human CD4-transgenic mice contributes to T cell decline upon intravenous administration of gp120.
The mechanisms accounting for T cell depletion in AIDS patients are not yet fully understood, nor are the roles of host factors in HIV pathogenesis. We show here that an ongoing humoral immune response to HIV gp120 can sensitize non-infected cells towards apoptosis. Thus, i.v. injection of 1 microg recombinant(r) gp120 into gp120-immunized human CD4-transgenic mice (huCD4 Tg), which express huCD4 on both T and B cells, results in T and B cell depletion in peripheral blood and lymphoid tissues. On day 6 after a bolus injection of gp120, the numbers of peripheral T cells and B cells in gp120-immunized huCD4 Tg decreased sevenfold and two- to threefold, respectively. Annexin V staining revealed a higher percentage of early apoptotic cells on day 1 of gp120 i.v. injection from gp120-primed huCD4 Tg spleens compared to gp120-primed controls. Boosting the primed huCD4 Tg mice with soluble gp120 and hen egg-white lysozyme led to lower secondary titers to both antigens than found in controls. Furthermore, splenocytes from gp120-pretreated immunized huCD4 Tg had a lower level of stimulation in response to anti-CD3 treatment. These in vivo results are consistent with in vitro data demonstrating that cross-linking CD4 on splenocytes of huCD4 Tg by rgp120SF2 and anti-gp120 not only sensitizes T cells for apoptosis, but also induces apoptosis per se, and suggest that anti-gp120 responsiveness can contribute to T cell depletion in AIDS.
Department of Immunology, American Red Cross, Rockville, MD 20855, USA.
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Y
Kang
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Melo
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Scott
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D017252:CD3 Complex / Q000276:immunology; D015704:CD4 Antigens / Q000235:genetics; D018791:CD4 Lymphocyte Count; D005260:Female; D015483:HIV Antibodies / Q000096:biosynthesis; D015699:HIV Envelope Protein gp120 / Q000008:administration & dosage / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology / Q000473:pathology; D006801:Humans; D007114:Immunization; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D008221:Lymphoid Tissue / Q000276:immunology / Q000473:pathology; D008231:Lymphopenia / Q000209:etiology / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009113:Muramidase / Q000276:immunology; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology
D017252:CD3 Complex; D015704:CD4 Antigens; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D011994:Recombinant Proteins; D009113:Muramidase