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Homeostatic cytokines orchestrate the segregation of CD4 and CD8 memory T-cell reservoirs in mice

Yang, Lili and Yu, Yang and Kalwani, Manorama and Tseng, Tai-Wei Joy and Baltimore, David (2011) Homeostatic cytokines orchestrate the segregation of CD4 and CD8 memory T-cell reservoirs in mice. Blood, 118 (11). pp. 3039-3050. ISSN 0006-4971. PMCID PMC3175781.

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Memory T cells (T_Ms) have been detected in many tissues but their quantitative distribution remains largely undefined. We show that in mice there is a remarkably biased accumulation of long-term CD4 T_Ms into mucosal sites (mainly gut, especially Peyer patches), and CD8 T_Ms into lymph nodes and spleen (in particular, peripheral lymph nodes [PLNs]). This distinction correlates with their differentiated expression of PLN- and gut-homing markers. CD8 and CD4 T_Ms selectively require the expression of PLN-homing marker CCR7 or gut-homing marker α4β7 for maintenance. PLNs and gut supply CD8 and CD4 T_Ms with their individually favored homeostatic cytokine, IL-15, or IL-7. Cytokine stimulation in turn regulates the different gut-homing marker expression on CD4 and CD8 T_Ms. IL-15 plays a major role in vivo regulating CD8 TMs homing to PLNs. Thus, the reservoir segregation of CD4 and CD8 T_Ms meets their individual needs for homeostatic cytokines and is under feedback control of cytokine stimulation.

Item Type:Article
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URLURL TypeDescription CentralArticle
Baltimore, David0000-0001-8723-8190
Additional Information:© 2011 by The American Society of Hematology. Submitted April 18, 2011; accepted July 7, 2011. Prepublished online as Blood First Edition paper, July 26, 2011. The authors thank Sarkis Mazmanian and June L. Round for technical advice, and Pin Wang, Dan Kahn, Xin Luo and Shengli Hao for critical reading of this manuscript and insightful discussions. This work was supported by the Skirball Foundation and National Institutes of Health P01 CA132681A. Authorship Contribution: L.Y. designed, performed and analyzed experiments, and wrote the paper; Y.Y., M.K., and T.-W.J.T. performed and analyzed experiments; and D.B. analyzed experiments and wrote the paper. Conflict-of-interest disclosure: The authors declare no competing financial interests. The current affiliation for T.-W.J.T. is Boehringer Ingelheim Pharmaceuticals Inc.
Funding AgencyGrant Number
Skirball FoundationUNSPECIFIED
NIHP01 CA 132681A
Issue or Number:11
PubMed Central ID:PMC3175781
Record Number:CaltechAUTHORS:20111003-111714898
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Official Citation:Lili Yang, Yang Yu, Manorama Kalwani, Tai-Wei Joy Tseng, and David Baltimore Homeostatic cytokines orchestrate the segregation of CD4 and CD8 memory T-cell reservoirs in mice Blood 2011 118:3039-3050; published ahead of print July 26, 2011, doi:10.1182/blood-2011-04-349746
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:25523
Deposited By: Ruth Sustaita
Deposited On:03 Oct 2011 18:45
Last Modified:16 Apr 2020 19:26

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