Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 206, Issue 5, Pages 991-999Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20090303
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Funding
- NIAID NIH HHS [AI072296, R01 AI076479, R01 AI032573, AI32573, AI076479, R56 AI032573, R01 AI072296, T32 AI049823] Funding Source: Medline
- PHS HHS [NIAID 155270] Funding Source: Medline
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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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