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

• DOI: 10.1084/jem.20090303
• Publication Date: 2009-05-11T18:43:39Z
• Authors: Arielle Glatman Z...; Justin J. Taylor; Irah L. King; Fraser A. Marshall; Markus Mohrs; Edward J. Pearce
• Keywords: CD4-Positive T-Lymphocytes; B-Lymphocytes; Interleukin-13; Brief Definitive Report; Helminthiasis; Cell Differentiation; Mice, Transgenic; T-Lymphocytes, Helper-Inducer; Immunoglobulin E; Schistosomiasis mansoni; 3. Good health; Mice; 03 medical and health sciences; Th2 Cells; 0302 clinical medicine; Genes, Reporter; T-Lymphocyte Subsets; Antigens, Helminth; Immunoglobulin G; Antibody Formation; Animals; Interleukin-4

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.