HIV-1-infected patients with envelope-specific lymphoproliferation or long-term nonprogression lack antibodies suppressing glycoprotein 120 antigen presentation

Peter C. Chien, Daniel Chen, Pei De Chen, Michael Tuen, Sandra Cohen, Stephen A. Migueles, Mark Connors, Eric Rosenberg, Uma Malhotra, Charles Gonzalez, Catarina E. Hioe

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7 Scopus citations

Abstract

Background. Antibodies to the CD4-binding domain (CD4bd) of human immunodeficiency virus type 1 (HIV-1) glycoprotein 120 (gp120) inhibit gp120 antigen presentation to CD4 T cells. These findings imply that the presence of anti-CD4bd antibodies might contribute to the dearth of envelope-specific T helper responses observed in most HIV-1-positive patients. In the absence of these antibodies, however, anti-envelope T helper responses might be maintained. Methods. We used ELISA to evaluate the levels of anti-CD4bd antibodies in rare HIV-1-positive patients who exhibit envelope-specific lymphoproliferation. Subsequently, we examined the contribution of anti-CD4bd antibodies to disease progression by comparing anti-CD4bd antibody levels in 3 cohorts of HIV-1-positive patients with distinct rates of disease progression. Results. Although most HIV-1-positive individuals produce anti-CD4bd antibodies, 77% of patients with envelope-specific lymphoproliferation have undetectable anti-CD4bd antibody levels. Moreover, comparison of the 3 HIV-1-positive cohorts revealed that individuals with long-term nonprogression have significantly lower anti-CD4bd antibody titers than do those with rapid or slow progression. Unlike immunoglobulin G (IgG) from rapid progressors, IgG from nonprogressors had no suppressive effects on glycoprotein (gp) 120-specific T cell proliferation. Conclusions. Low anti-CD4bd antibody levels are associated with the absence of disease progression. A number of HIV-1-positive individuals without these antibodies also appear to sustain gp120-specific T helper responses needed to help control the infection.

Original languageEnglish
Pages (from-to)852-861
Number of pages10
JournalJournal of Infectious Diseases
Volume189
Issue number5
DOIs
StatePublished - 1 Mar 2004
Externally publishedYes

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