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

Immunol Cell Biol. 2009 Nov-Dec;87(8):590-600. doi: 10.1038/icb.2009.64. Epub 2009 Sep 1.


T follicular helper (T(FH)) 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 T(FH) cells are the expressions of CXCR5, ICOS, interleukin (IL)-21 and BCL-6. The requirements for human T(FH) 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-gamma 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 T(FH) cell fate, and thus underpin antibody-mediated immunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Differentiation
  • Cell Lineage*
  • Cells, Cultured
  • Coculture Techniques
  • Dendritic Cells / immunology
  • Humans
  • Immunity, Innate*
  • Interleukin-12 / immunology*
  • Interleukins / immunology
  • Lymphoid Tissue / immunology*
  • Phenotype
  • T-Lymphocytes, Helper-Inducer / cytology
  • T-Lymphocytes, Helper-Inducer / immunology*


  • Interleukins
  • Interleukin-12
  • interleukin-21