T follicular helper cells differentiate from Th2 cells in response to helminth antigens.
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.
Glatman Zaretsky
Arielle
A
Department of Pathobiology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Taylor
Justin J
JJ
King
Irah L
IL
Marshall
Fraser A
FA
Mohrs
Markus
M
Pearce
Edward J
EJ
D000818:Animals; D000917:Antibody Formation; D000947:Antigens, Helminth / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D017930:Genes, Reporter; D006373:Helminthiasis / Q000276:immunology*; D007073:Immunoglobulin E / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D018793:Interleukin-13 / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D012555:Schistosomiasis mansoni / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology*
D000947:Antigens, Helminth; D007074:Immunoglobulin G; D018793:Interleukin-13; D015847:Interleukin-4; D007073:Immunoglobulin E