In:
The Journal of Immunology, The American Association of Immunologists, Vol. 188, No. 4 ( 2012-02-15), p. 2001-2013
Abstract:
CD69 is highly expressed by lymphocytes at mucosal surfaces. We aimed to investigate the role of CD69 in mucosal immune responses. The expression of CD69 by CD4 T cells isolated from the spleen, mesenteric lymph nodes, small intestinal lamina propria, and colonic lamina propria was determined in specific pathogen-free B6 and TCR transgenic animals, as well as in germ-free B6 mice. Transfer colitis was induced by transplanting RAG−/− mice with B6 or CD69−/−CD45RBhigh CD4 T cells. CD69 expression by CD4 T cells is induced by the intestinal microflora, oral delivery of specific Ag, and type I IFN (IFN-I) signals. CD4 T cells from CD69−/− animals produce higher amounts of the proinflammatory cytokines IFN-γ, TNF-α, and IL-21, whereas the production of TGF-β1 is decreased. CD69-deficient CD4 T cells showed reduced potential to differentiate into Foxp3+ regulatory T cells in vivo and in vitro. The transfer of CD69−/−CD45RBhigh CD4 T cells into RAG−/− hosts induced an accelerated colitis. Oral tolerance was impaired in CD69−/− and IFN-I receptor 1-deficient mice when compared with B6 and OT-II × RAG−/− animals. Polyinosinic-polycytidylic acid treatment of RAG−/− mice transplanted with B6 but not CD69−/− or IFN-I receptor 1-deficient CD45RBhigh CD4 T cells attenuated transfer colitis. CD69 deficiency led to the increased production of proinflammatory cytokines, reduced Foxp3+ regulatory T cell induction, impaired oral tolerance, and more severe colitis. Hence, the activation Ag CD69 plays an important role in regulating mucosal immune responses.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.1100765
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2012
detail.hit.zdb_id:
1475085-5
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