CD4 epitope masking by gp120/anti-gp120 antibody complexes. A potential mechanism for CD4+ cell function down-regulation in AIDS patients.
The in vitro suppressive effect of gp120 and gp120/anti-gp120 antibody is well known but not yet proven to operate in vivo. We report findings consistent with the presence of gp120/anti-gp120 antibody complexes on CD4+ lymphocytes from HIV-infected patients with advanced disease. PBMC from most AIDS patients showed selective masking of the CD4 epitope associated with the gp120 binding site; immunoprecipitation of PBMC with anti-CD4 mAb disclosed high amounts of IgG bound to CD4 receptors. Antibodies against HIV env proteins, but not other HIV products or CD4 Ag, were detected in purified CD4+ cell culture supernatants; in vitro culture was associated with normalization of both CD4 expression in PBMC and the lymphocyte proliferative response to anti-CD3. gp120 presence could not be directly demonstrated, but findings strongly suggested that CD4+ lymphocytes from most HIV-infected patients with advanced disease were covered with gp120/anti-gp120 antibody complexes, which are responsible for down-regulation of surface CD4 expression as well as functional lymphocyte impairment; this event may represent an important mechanism in the pathogenesis of HIV-associated immunodeficiency.
Amadori
A
A
Institute of Oncology, University of Padua, Italy.
De Silvestro
G
G
Zamarchi
R
R
Veronese
M L
ML
Mazza
M R
MR
Schiavo
G
G
Panozzo
M
M
De Rossi
A
A
Ometto
L
L
Mous
J
J
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology*; D000918:Antibody Specificity; D000936:Antigen-Antibody Complex / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis / Q000276:immunology; D018801:CD2 Antigens; D017252:CD3 Complex; D015704:CD4 Antigens / Q000096:biosynthesis / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016827:CD8 Antigens / Q000096:biosynthesis; D015536:Down-Regulation / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D005434:Flow Cytometry; D015967:Gene Expression Regulation, Viral; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D066298:In Vitro Techniques; D008213:Lymphocyte Activation / Q000276:immunology; D011233:Precipitin Tests; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D011971:Receptors, Immunologic / Q000096:biosynthesis
D000936:Antigen-Antibody Complex; D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D000939:Epitopes; D015699:HIV Envelope Protein gp120; D007074:Immunoglobulin G; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic