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PLoS Pathog. 2014 Jan 30;10(1):e1003853. doi: 10.1371/journal.ppat.1003853. eCollection 2014 Jan.

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

Author information

1
Immunology Laboratory, Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America.
2
Immunology Laboratory, Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America ; United States Military HIV Research Program, Rockville, Maryland, United States of America.
3
Human Immunology Section, Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America.
4
Immunology Core Section, Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America.
5
ImmunoTechnology Section, Vaccine Research Center, National Institutes of Health, Bethesda, Maryland, United States of America.
6
Division of Infectious Diseases, Antiviral Research Center, University of California San Diego, San Diego, California, United States of America.
7
HIV-Specific Immunity Section, Laboratory of Immunoregulation, NIAID, NIH, Bethesda, Maryland, United States of America.
8
United States Military HIV Research Program, Rockville, Maryland, United States of America.

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.

PMID:
24497824
PMCID:
PMC3911819
DOI:
10.1371/journal.ppat.1003853
[Indexed for MEDLINE]
Free PMC Article

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