Details

Autor(en) / Beteiligte

• Boswell, Kristin L
• Paris, Robert
• Boritz, Eli
• Ambrozak, David
• Yamamoto, Takuya
• Darko, Sam
• Wloka, Kaska
• Wheatley, Adam
• Narpala, Sandeep
• McDermott, Adrian
• Roederer, Mario
• Haubrich, Richard
• Connors, Mark
• Ake, Julie
• Douek, Daniel C
• Kim, Jerome
• Petrovas, Constantinos
• Koup, Richard A
• Silvestri, Guido

Titel

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

Ist Teil von

• PLoS pathogens, 2014-01, Vol.10 (1), p.e1003853-e1003853

Ort / Verlag

United States: Public Library of Science

Erscheinungsjahr

2014

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.