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Early commitment of naïve human CD4+ T cells to the T follicular helper (TFH) cell lineage is induced by IL-12.

Authors :
Ma, Cindy S.
Suryani, Santi
Avery, Danielle T.
Chan, Anna
Nanan, Ralph
Santner-Nanan, Brigitte
Deenick, Elissa K.
Tangye, Stuart G.
Source :
Immunology & Cell Biology. Nov/Dec2009, Vol. 87 Issue 8, p590-600. 11p. 1 Chart, 6 Graphs.
Publication Year :
2009

Abstract

T follicular helper (TFH) cells are a specialized subset of CD4+ T cells that localize to B-cell follicles, where they are positioned to provide help for the induction of optimal humoral immune responses. Key features of TFH cells are the expressions of CXCR5, ICOS, interleukin (IL)-21 and BCL-6. The requirements for human TFH cell development are unknown. Here we show that IL-6, IL-12, IL-21 and IL-23 are capable of inducing IL-21 expression in naïve CD4+ T cells isolated from human tonsils, peripheral blood and cord blood. However, only IL-12 induced sustained expressions of CXCR5 and ICOS on these activated naïve CD4+ T cells, and endowed them with the ability to provide increased help to B cells for their differentiation into immunoglobulin-secreting cells. The effects of IL-12 were independent of interferon-γ and T-bet, and associated with upregulation of BCL-6 expression. Thus, these cytokines, particularly IL-12, are likely to act at an early stage during dendritic cell-mediated priming of naïve CD4+ T cells into a TFH cell fate, and thus underpin antibody-mediated immunity. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
08189641
Volume :
87
Issue :
8
Database :
Academic Search Index
Journal :
Immunology & Cell Biology
Publication Type :
Academic Journal
Accession number :
45117867
Full Text :
https://doi.org/10.1038/icb.2009.64