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CD4 epitope masking by gp120/anti-gp120 antibody complexes. A potential mechanism for CD4+ cell function
A Amadori1, G De Silvestro, R Zamarchi
1Institute of Oncology, University of Padua, Italy.
Insights
Immune complexes of gp120 and antibodies bind to CD4+ lymphocytes in advanced HIV disease. This binding impairs immune cell function and CD4 expression, contributing to immunodeficiency.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- The in vitro suppressive effects of gp120 and gp120/anti-gp120 antibody complexes on immune cells are established.
- However, the in vivo relevance of these suppressive effects in human immunodeficiency virus (HIV) infection has not been definitively proven.
Purpose of the Study:
- To investigate the presence and functional impact of gp120/anti-gp120 antibody complexes on CD4+ lymphocytes in HIV-infected patients with advanced disease.
- To explore the potential role of these complexes in the pathogenesis of HIV-associated immunodeficiency.
Main Methods:
- Analysis of peripheral blood mononuclear cells (PBMCs) from AIDS patients.
- Immunoprecipitation of PBMCs using anti-CD4 monoclonal antibodies (mAbs).
- Detection of antibodies against HIV env proteins in CD4+ cell culture supernatants.
Main Results:
- PBMCs from most AIDS patients exhibited selective masking of the CD4 epitope, indicating gp120 binding.
- High levels of IgG were found bound to CD4 receptors on CD4+ lymphocytes.
- Antibodies against HIV env proteins were detected, but not against other HIV products or CD4 antigens.
- In vitro culture led to normalization of CD4 expression and lymphocyte proliferative responses.
Conclusions:
- Findings strongly suggest that CD4+ lymphocytes in advanced HIV disease are coated with gp120/anti-gp120 antibody complexes.
- These complexes likely cause the down-regulation of surface CD4 expression and functional lymphocyte impairment.
- This mechanism may be crucial in the pathogenesis of HIV-associated immunodeficiency.
Abstract:
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.