Loss of circulating CD4 T cells with B cell helper function during chronic HIV infection.

TitleLoss of circulating CD4 T cells with B cell helper function during chronic HIV infection.
Publication TypeJournal Article
Year of Publication2014
AuthorsBoswell KL, Paris R, Boritz E, Ambrozak D, Yamamoto T, Darko S, Wloka K, Wheatley A, Narpala S, McDermott A, Roederer M, Haubrich R, Connors M, Ake J, Douek DC, Kim J, Petrovas C, Koup RA
JournalPLoS Pathog
Volume10
Issue1
Paginatione1003853
Date Published2014 Jan
ISSN1553-7374
KeywordsAdult, Antibodies, Neutralizing, Antigens, Differentiation, B-Lymphocytes, Chronic Disease, Female, HIV Antibodies, HIV Infections, Humans, Immunologic Memory, Male, T-Lymphocytes, Helper-Inducer
Abstract

The interaction between follicular T helper cells (TFH) and B cells in the lymph nodes and spleen has a major impact on the development of antigen-specific B cell responses during infection or vaccination. Recent studies described a functional equivalent of these cells among circulating CD4 T cells, referred to as peripheral TFH cells. Here, we characterize the phenotype and in vitro B cell helper activity of peripheral TFH populations, as well as the effect of HIV infection on these populations. In co-culture experiments we confirmed CXCR5+ cells from HIV-uninfected donors provide help to B cells and more specifically, we identified a CCR7(high)CXCR5(high)CCR6(high)PD-1(high) CD4 T cell population that secretes IL-21 and enhances isotype-switched immunoglobulin production. This population is significantly decreased in treatment-naïve, HIV-infected individuals and can be recovered after anti-retroviral therapy. We found impaired immunoglobulin production in co-cultures from HIV-infected individuals and found no correlation between the frequency of peripheral TFH cells and memory B cells, or with neutralization activity in untreated HIV infection in our cohort. Furthermore, we found that within the peripheral TFH population, the expression level of TFH-associated genes more closely resembles a memory, non-TFH population, as opposed to a TFH population. Overall, our data identify a heterogeneous population of circulating CD4 T cells that provides in vitro help to B cells, and challenges the origin of these cells as memory TFH cells.

DOI10.1371/journal.ppat.1003853
Alternate JournalPLoS Pathog.
PubMed ID24497824
PubMed Central IDPMC3911819
Grant ListAI064086 / AI / NIAID NIH HHS / United States
AI36214 / AI / NIAID NIH HHS / United States
AI69432 / AI / NIAID NIH HHS / United States
G12 RR003048 / RR / NCRR NIH HHS / United States
K24 AI064086 / AI / NIAID NIH HHS / United States
P30 AI036214 / AI / NIAID NIH HHS / United States
P30 AI087714 / AI / NIAID NIH HHS / United States
P30AI087714 / AI / NIAID NIH HHS / United States
Y1-AI-2642-12 / AI / NIAID NIH HHS / United States
/ / Intramural NIH HHS / United States