Antigen-Bearing Dendritic Cells Regulate the Diverse Pattern of Memory CD8 T Cell Development in Different Tissues

Memory T cells of the effector type (TEM) account for the characteristic rapidity of memory T-cell responses, whereas memory T cells of the central type (TCM) account for long-lasting, vigorously proliferating memory T-cell responses. How antigen-stimulated (primed) T cells develop into different me...

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Main Authors: Shen, Ching-Hung, Talay, Oezcan, Mahajan, Vinay S., Leskov, Ilya B., Eisen, Herman N., Chen, Jianzhu
Other Authors: Massachusetts Institute of Technology. Department of Biology
Format: Article
Language:en_US
Published: National Academy of Sciences (U.S.) 2011
Online Access:http://hdl.handle.net/1721.1/64806
https://orcid.org/0000-0002-5687-6154
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author Shen, Ching-Hung
Talay, Oezcan
Mahajan, Vinay S.
Leskov, Ilya B.
Eisen, Herman N.
Chen, Jianzhu
author2 Massachusetts Institute of Technology. Department of Biology
author_facet Massachusetts Institute of Technology. Department of Biology
Shen, Ching-Hung
Talay, Oezcan
Mahajan, Vinay S.
Leskov, Ilya B.
Eisen, Herman N.
Chen, Jianzhu
author_sort Shen, Ching-Hung
collection MIT
description Memory T cells of the effector type (TEM) account for the characteristic rapidity of memory T-cell responses, whereas memory T cells of the central type (TCM) account for long-lasting, vigorously proliferating memory T-cell responses. How antigen-stimulated (primed) T cells develop into different memory T-cell subsets with diverse tissue distributions is largely unknown. Here we show that after respiratory tract infection of mice with influenza virus, viral antigen associated with dendritic cells (DCs) was abundant in lung-draining lymph nodes (DLN) and the spleen for more than a week but was scant and transient in nondraining lymph nodes (NDLN). Correspondingly, activated CD8 T cells proliferated extensively in DLN and the spleen but minimally in NDLN. Strikingly, however, although most persisting CD8 T cells in DLN and spleen exhibited the TEM phenotype, those persisting in NDLN exhibited the TCM phenotype. Reducing antigen exposure by depleting DCs at the peak of primary T-cell responses enhanced the development of TCM, whereas subjecting primed CD8 T cells from NDLN to additional antigen stimulation inhibited TCM development. These findings demonstrate that differences in persistence of antigen-bearing DCs in various tissues regulate the tissue-specific pattern of memory CD8 T-cell development. The findings have significant implications for design of vaccines and immunization strategies.
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spelling mit-1721.1/648062022-09-29T21:22:24Z Antigen-Bearing Dendritic Cells Regulate the Diverse Pattern of Memory CD8 T Cell Development in Different Tissues Shen, Ching-Hung Talay, Oezcan Mahajan, Vinay S. Leskov, Ilya B. Eisen, Herman N. Chen, Jianzhu Massachusetts Institute of Technology. Department of Biology Koch Institute for Integrative Cancer Research at MIT Chen, Jianzhu Chen, Jianzhu Shen, Ching-Hung Talay, Oezcan Mahajan, Vinay S. Leskov, Ilya B. Eisen, Herman N. Memory T cells of the effector type (TEM) account for the characteristic rapidity of memory T-cell responses, whereas memory T cells of the central type (TCM) account for long-lasting, vigorously proliferating memory T-cell responses. How antigen-stimulated (primed) T cells develop into different memory T-cell subsets with diverse tissue distributions is largely unknown. Here we show that after respiratory tract infection of mice with influenza virus, viral antigen associated with dendritic cells (DCs) was abundant in lung-draining lymph nodes (DLN) and the spleen for more than a week but was scant and transient in nondraining lymph nodes (NDLN). Correspondingly, activated CD8 T cells proliferated extensively in DLN and the spleen but minimally in NDLN. Strikingly, however, although most persisting CD8 T cells in DLN and spleen exhibited the TEM phenotype, those persisting in NDLN exhibited the TCM phenotype. Reducing antigen exposure by depleting DCs at the peak of primary T-cell responses enhanced the development of TCM, whereas subjecting primed CD8 T cells from NDLN to additional antigen stimulation inhibited TCM development. These findings demonstrate that differences in persistence of antigen-bearing DCs in various tissues regulate the tissue-specific pattern of memory CD8 T-cell development. The findings have significant implications for design of vaccines and immunization strategies. National Institutes of Health (U.S.) (Grant AI69208) Singapore-MIT Alliance National Cancer Institute (U.S.) 2011-07-14T15:06:42Z 2011-07-14T15:06:42Z 2010-12 2010-07 Article http://purl.org/eprint/type/JournalArticle 0027-8424 1091-6490 http://hdl.handle.net/1721.1/64806 Shen, Ching-Hung et al. “Antigen-bearing Dendritic Cells Regulate the Diverse Pattern of Memory CD8 T-cell Development in Different Tissues.” Proceedings of the National Academy of Sciences 107.52 (2010) : 22587 -22592. https://orcid.org/0000-0002-5687-6154 en_US http://dx.doi.org/10.1073/pnas.1016350108 Proceedings of the National Academy of Sciences of the United States of America Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf National Academy of Sciences (U.S.) PNAS
spellingShingle Shen, Ching-Hung
Talay, Oezcan
Mahajan, Vinay S.
Leskov, Ilya B.
Eisen, Herman N.
Chen, Jianzhu
Antigen-Bearing Dendritic Cells Regulate the Diverse Pattern of Memory CD8 T Cell Development in Different Tissues
title Antigen-Bearing Dendritic Cells Regulate the Diverse Pattern of Memory CD8 T Cell Development in Different Tissues
title_full Antigen-Bearing Dendritic Cells Regulate the Diverse Pattern of Memory CD8 T Cell Development in Different Tissues
title_fullStr Antigen-Bearing Dendritic Cells Regulate the Diverse Pattern of Memory CD8 T Cell Development in Different Tissues
title_full_unstemmed Antigen-Bearing Dendritic Cells Regulate the Diverse Pattern of Memory CD8 T Cell Development in Different Tissues
title_short Antigen-Bearing Dendritic Cells Regulate the Diverse Pattern of Memory CD8 T Cell Development in Different Tissues
title_sort antigen bearing dendritic cells regulate the diverse pattern of memory cd8 t cell development in different tissues
url http://hdl.handle.net/1721.1/64806
https://orcid.org/0000-0002-5687-6154
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