Induction of CD4+ T cell depletion in mice doubly transgenic for HIV gp120 and human CD4.
It has been suggested that loss of uninfected T cells in HIV infection occurs because of lymphocyte activation resulting in cell death by apoptosis. To address the question of whether cross-linking of CD4/HIV gp120 complexes by antibodies were sufficient to induce T cell depletion in vivo, we developed an animal model of continuous interaction between human CD4 (hCD4), gp120 and anti-gp120 antibodies in the absence of other viral factors. Double-transgenic mice have been generated in which T cells express on their membrane hCD4 and secrete HIV gp120. Although these mice have hCD4/gp120 complexes present on the surface of T cells, they do not show gross immunological abnormalities, and they are able to produce anti-gp120 antibodies following immunization with denaturated gp120. However, double-transgenic mice with antibodies to gp120, when immunized with tetanus toxoid, mount an IgG response that is significantly lower than that of double-transgenic mice without antibodies to gp120. Furthermore, the presence of anti-gp120 antibodies leads 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.
Finco
O
O
Chiron-Vaccines Immunobiology Research Institute, Siena, Italy.
Nuti
S
S
De Magistris
M T
MT
Mangiavacchi
L
L
Aiuti
A
A
Forte
P
P
Fantoni
A
A
van der Putten
H
H
Abrignani
S
S
D000818:Animals; D000914:Antibodies, Viral / Q000494:pharmacology; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D015704:CD4 Antigens / Q000235:genetics*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000502:physiology; D003433:Crosses, Genetic; D005260:Female; D015699:HIV Envelope Protein gp120 / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008136:Longevity / Q000235:genetics / Q000276:immunology; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011485:Protein Binding / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology
D000914:Antibodies, Viral; D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D011993:Recombinant Fusion Proteins