IL-4–producing CD4+ T cells in reactive lymph nodes during helminth infection are T follicular helper cells
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Open Access
- 20 April 2009
- journal article
- Published by Rockefeller University Press in The Journal of Experimental Medicine
- Vol. 206 (5), 1001-1007
- https://doi.org/10.1084/jem.20090313
Abstract
Interleukin (IL)-4 is the quintessential T helper type 2 (Th2) cytokine produced by CD4(+) T cells in response to helminth infection. IL-4 not only promotes the differentiation of Th2 cells but is also critical for immunoglobulin (Ig) G1 and IgE isotype-switched antibody responses. Despite the IL-4-mediated link between Th2 cells and B lymphocytes, the location of IL-4-producing T cells in the lymph nodes is currently unclear. Using IL-4 dual reporter mice, we examined the Th2 response and IL-4 production in the draining mesenteric lymph nodes during infection with the enteric nematode Heligmosomoides polygyrus. We show that although IL-4-competent Th2 cells are found throughout the B and T cell areas, IL-4-producing Th2 cells are restricted to the B cell follicles and associate with germinal centers. Consistent with their localization, IL-4 producers express high levels of CXCR5, ICOS, PD-1, IL-21, and BCL-6, a phenotype characteristic of T follicular helper (Tfh) cells. Although IL-4 was dispensable for the generation of Th2 and Tfh cells, its deletion resulted in defective B cell expansion and maturation. Our report reveals the compartmentalization of Th2 priming and IL-4 production in the lymph nodes during infection, and identifies Tfh cells as the dominant source of IL-4 in vivo.Keywords
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