作者
Kristin L Boswell, Robert Paris, Eli Boritz, David Ambrozak, Takuya Yamamoto, Sam Darko, Kaska Wloka, Adam Wheatley, Sandeep Narpala, Adrian McDermott, Mario Roederer, Richard Haubrich, Mark Connors, Julie Ake, Daniel C Douek, Jerome Kim, Constantinos Petrovas, Richard A Koup
发表日期
2014/1/30
期刊
PLoS pathogens
卷号
10
期号
1
页码范围
e1003853
出版商
Public Library of Science
简介
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 CCR7highCXCR5highCCR6highPD-1high 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.
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