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Adaptive immune cells temper initial innate responses

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(1,2,3,4). Lymphocyte-d...

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Autores principales: Dong Kim, Kwang, Zhao, Jie, Auh, Sogyong, Yang, Xuanming, Du, Peishuang, Tang, Hong, Fu, Yang-Xin
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group US 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2435248/
https://www.ncbi.nlm.nih.gov/pubmed/17891146
http://dx.doi.org/10.1038/nm1633
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author Dong Kim, Kwang
Zhao, Jie
Auh, Sogyong
Yang, Xuanming
Du, Peishuang
Tang, Hong
Fu, Yang-Xin
author_facet Dong Kim, Kwang
Zhao, Jie
Auh, Sogyong
Yang, Xuanming
Du, Peishuang
Tang, Hong
Fu, Yang-Xin
author_sort Dong Kim, Kwang
collection PubMed
description 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(1,2,3,4). 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. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nm1633) contains supplementary material, which is available to authorized users.
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spelling pubmed-24352482008-06-22 Adaptive immune cells temper initial innate responses Dong Kim, Kwang Zhao, Jie Auh, Sogyong Yang, Xuanming Du, Peishuang Tang, Hong Fu, Yang-Xin Nat Med Article 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(1,2,3,4). 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. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nm1633) contains supplementary material, which is available to authorized users. Nature Publishing Group US 2007-09-23 2007 /pmc/articles/PMC2435248/ /pubmed/17891146 http://dx.doi.org/10.1038/nm1633 Text en © Nature Publishing Group 2007 This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
spellingShingle Article
Dong Kim, Kwang
Zhao, Jie
Auh, Sogyong
Yang, Xuanming
Du, Peishuang
Tang, Hong
Fu, Yang-Xin
Adaptive immune cells temper initial innate responses
title Adaptive immune cells temper initial innate responses
title_full Adaptive immune cells temper initial innate responses
title_fullStr Adaptive immune cells temper initial innate responses
title_full_unstemmed Adaptive immune cells temper initial innate responses
title_short Adaptive immune cells temper initial innate responses
title_sort adaptive immune cells temper initial innate responses
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2435248/
https://www.ncbi.nlm.nih.gov/pubmed/17891146
http://dx.doi.org/10.1038/nm1633
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