HIV-1 antibody neutralization breadth is associated with enhanced HIV-specific CD4+ T cell responses.

TitleHIV-1 antibody neutralization breadth is associated with enhanced HIV-specific CD4+ T cell responses.
Publication TypeJournal Article
Year of Publication2015
AuthorsRanasinghe S, Soghoian DZ, Lindqvist M, Ghebremichael M, Donaghey F, Carrington M, Seaman MS, Kaufmann DE, Walker BD, Porichis F
JournalJ Virol
Date Published12/09/2015
ISSN1098-5514
Abstract

Antigen-specific CD4+ T helper cell responses have long been recognized to be a critical component of effective vaccine immunity. CD4+ T cells are necessary to generate and maintain humoral immune responses by providing help to antigen-specific B cells for the production of antibodies. In HIV infection, CD4+ T cells are thought to be necessary for the induction of Env-specific broadly neutralizing antibodies. However, few studies have investigated the role of HIV-specific CD4+ T cells in association with HIV neutralizing antibody activity in vaccination or natural infection settings. Here we conducted a comprehensive analysis of HIV-specific CD4+ T cell responses in a cohort of 34 untreated HIV-infected viremic controllers matched for viral load, with and without neutralizing antibody breadth to a panel of viral strains. Our results show that the breadth and magnitude of Gag-specific CD4+ T cell responses were significantly higher in individuals with neutralizing antibodies versus those without neutralizing antibodies. The breadth of Gag-specific CD4+ T cell responses was positively correlated with the breadth of neutralizing antibody activity. Furthermore, the breadth and magnitude of gp41-specific, but not gp120-specific, CD4+ T cell responses were significantly elevated in individuals with neutralizing antibodies. Together, these data suggest that robust Gag-specific CD4+ T cells, and to a lesser extent, gp41-specific CD4+ T cells, may provide important intermolecular help to Env-specific B cells that promote the generation or maintenance of Env-specific neutralizing antibodies.

IMPORTANCE: One of the earliest discoveries related to CD4+ T cell function was their provision of help to B cells in the development of antibody responses. Yet, little is known about the role of CD4+ T helper responses in the setting of HIV infection, and no studies to date have evaluated the impact of HIV-specific CD4+ T cells on the generation of antibodies that can neutralize multiple different strains of HIV. Here, we addressed this question by analyzing HIV-specific CD4+ T cell responses in untreated HIV-infected persons with and without neutralizing antibodies. Our results indicate that HIV-infected persons with neutralizing antibodies have significantly more robust CD4+ T cell responses targeting Gag and gp41 proteins when compared with individuals that lack neutralizing antibodies. These associations suggest that Gag- and gp41-specific CD4+ T cell responses may provide robust help to B cells for the generation or maintenance of neutralizing antibodies in natural HIV-infection.

DOI10.1128/JVI.02278-15
Alternate JournalJ. Virol.
PubMed ID26656715
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