T follicular helper cells differentiate from Th2 cells in response to helminth antigens

AG Zaretsky, JJ Taylor, IL King, FA Marshall… - Journal of Experimental …, 2009 - rupress.org
AG Zaretsky, JJ Taylor, IL King, FA Marshall, M Mohrs, EJ Pearce
Journal of Experimental Medicine, 2009rupress.org
The relationship of T follicular helper (TFH) cells to other T helper (Th) subsets is
controversial. We find that after helminth infection, or immunization with helminth antigens,
reactive lymphoid organs of 4get IL-4/GFP reporter mice contain populations of IL-4/GFP-
expressing CD4+ T cells that display the TFH markers CXCR5, PD-1, and ICOS. These TFH
cells express the canonical TFH markers BCL6 and IL-21, but also GATA3, the master
regulator of Th2 cell differentiation. Consistent with a relationship between Th2 and TFH …
The relationship of T follicular helper (TFH) cells to other T helper (Th) subsets is controversial. We find that after helminth infection, or immunization with helminth antigens, reactive lymphoid organs of 4get IL-4/GFP reporter mice contain populations of IL-4/GFP-expressing CD4+ T cells that display the TFH markers CXCR5, PD-1, and ICOS. These TFH cells express the canonical TFH markers BCL6 and IL-21, but also GATA3, the master regulator of Th2 cell differentiation. Consistent with a relationship between Th2 and TFH cells, IL-4 protein production, reported by expression of huCD2 in IL-4 dual reporter (4get/KN2) mice, was a robust marker of TFH cells in LNs responding to helminth antigens. Moreover, the majority of huCD2/IL-4–producing Th cells were found within B cell follicles, consistent with their definition as TFH cells. TFH cell development after immunization failed to occur in mice lacking B cells or CD154. The relationship of TFH cells to the Th2 lineage was confirmed when TFH cells were found to develop from CXCR5 PD-1 IL-4/GFP+ CD4+ T cells after their transfer into naive mice and antigen challenge in vivo.
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