Adaptive immune cells temper initial innate responses

Kwang Dong Kim, Jie Zhao, Sogyong Auh, Xuanming Yang, Peishuang Du, Hong Tang, Yang Xin Fu

Research output: Contribution to journalArticle

202 Scopus citations

Abstract

Toll-like receptors (TLRs) recognize conserved microbial structures called pathogen-associated molecular patterns. Signaling from TLRs leads to upregulation of co-stimulatory molecules for better priming of T cells and secretion of inflammatory cytokines by innate immune cells. Lymphocyte-deficient hosts often die of acute infection, presumably owing to their lack of an adaptive immune response to effectively clear pathogens. However, we show here that an unleashed innate immune response due to the absence of residential T cells can also be a direct cause of death. Viral infection or administration of poly(I:C), a ligand for TLR3, led to cytokine storm in T-cell- or lymphocyte-deficient mice in a fashion dependent on NK cells and tumor necrosis factor. We have further shown, through the depletion of CD4+ and CD8+ cells in wild-type mice and the transfer of T lymphocytes into Rag-1-deficient mice, respectively, that T cells are both necessary and sufficient to temper the early innate response. In addition to the effects of natural regulatory T cells, close contact of resting CD4+CD25 -Foxp3- or CD8+ T cells with innate cells could also suppress the cytokine surge by various innate cells in an antigen-independent fashion. Therefore, adaptive immune cells have an unexpected role in tempering initial innate responses.

Original languageEnglish (US)
Pages (from-to)1248-1252
Number of pages5
JournalNature medicine
Volume13
Issue number10
DOIs
StatePublished - Oct 1 2007

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Dong Kim, K., Zhao, J., Auh, S., Yang, X., Du, P., Tang, H., & Fu, Y. X. (2007). Adaptive immune cells temper initial innate responses. Nature medicine, 13(10), 1248-1252. https://doi.org/10.1038/nm1633