A critical role for CD8 T cells in a nonhuman primate model of tuberculosis
The role of CD8 T cells in anti-tuberculosis immunity in humans remains unknown, and studies of CD8 T cell-mediated protection against tuberculosis in mice have yielded controversial results. Unlike mice, humans and nonhuman primates share a number of important features of the immune system that rel...
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| Veröffentlicht in: | PLoS pathogens 2009-04, Vol.5 (4), p.e1000392-e1000392 |
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| creator | Chen, Crystal Y Huang, Dan Wang, Richard C Shen, Ling Zeng, Gucheng Yao, Shuyun Shen, Yun Halliday, Lisa Fortman, Jeff McAllister, Milton Estep, Jim Hunt, Robert Vasconcelos, Daphne Du, George Porcelli, Steven A Larsen, Michelle H Jacobs, Jr, William R Haynes, Barton F Letvin, Norman L Chen, Zheng W |
| description | The role of CD8 T cells in anti-tuberculosis immunity in humans remains unknown, and studies of CD8 T cell-mediated protection against tuberculosis in mice have yielded controversial results. Unlike mice, humans and nonhuman primates share a number of important features of the immune system that relate directly to the specificity and functions of CD8 T cells, such as the expression of group 1 CD1 proteins that are capable of presenting Mycobacterium tuberculosis lipids antigens and the cytotoxic/bactericidal protein granulysin. Employing a more relevant nonhuman primate model of human tuberculosis, we examined the contribution of BCG- or M. tuberculosis-elicited CD8 T cells to vaccine-induced immunity against tuberculosis. CD8 depletion compromised BCG vaccine-induced immune control of M. tuberculosis replication in the vaccinated rhesus macaques. Depletion of CD8 T cells in BCG-vaccinated rhesus macaques led to a significant decrease in the vaccine-induced immunity against tuberculosis. Consistently, depletion of CD8 T cells in rhesus macaques that had been previously infected with M. tuberculosis and cured by antibiotic therapy also resulted in a loss of anti-tuberculosis immunity upon M. tuberculosis re-infection. The current study demonstrates a major role for CD8 T cells in anti-tuberculosis immunity, and supports the view that CD8 T cells should be included in strategies for development of new tuberculosis vaccines and immunotherapeutics. |
| doi_str_mv | 10.1371/journal.ppat.1000392 |
| format | Article |
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Unlike mice, humans and nonhuman primates share a number of important features of the immune system that relate directly to the specificity and functions of CD8 T cells, such as the expression of group 1 CD1 proteins that are capable of presenting Mycobacterium tuberculosis lipids antigens and the cytotoxic/bactericidal protein granulysin. Employing a more relevant nonhuman primate model of human tuberculosis, we examined the contribution of BCG- or M. tuberculosis-elicited CD8 T cells to vaccine-induced immunity against tuberculosis. CD8 depletion compromised BCG vaccine-induced immune control of M. tuberculosis replication in the vaccinated rhesus macaques. Depletion of CD8 T cells in BCG-vaccinated rhesus macaques led to a significant decrease in the vaccine-induced immunity against tuberculosis. Consistently, depletion of CD8 T cells in rhesus macaques that had been previously infected with M. tuberculosis and cured by antibiotic therapy also resulted in a loss of anti-tuberculosis immunity upon M. tuberculosis re-infection. The current study demonstrates a major role for CD8 T cells in anti-tuberculosis immunity, and supports the view that CD8 T cells should be included in strategies for development of new tuberculosis vaccines and immunotherapeutics.</description><identifier>ISSN: 1553-7374</identifier><identifier>ISSN: 1553-7366</identifier><identifier>EISSN: 1553-7374</identifier><identifier>DOI: 10.1371/journal.ppat.1000392</identifier><identifier>PMID: 19381260</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Acquired immune deficiency syndrome ; AIDS ; Animals ; BCG Vaccine - immunology ; CD8 Antigens - immunology ; CD8 lymphocytes ; CD8-Positive T-Lymphocytes - immunology ; Cytotoxicity ; Disease Models, Animal ; Genetic aspects ; Health aspects ; Human immunodeficiency virus ; Humans ; Immunology/Immunity to Infections ; Infections ; Infectious Diseases ; Lymphocytes ; Macaca mulatta ; Multivariate analysis ; Mycobacterium tuberculosis ; Mycobacterium tuberculosis - immunology ; Mycobacterium tuberculosis - physiology ; Pathology ; Prevention ; Primates ; Risk factors ; Tuberculosis ; Tuberculosis - immunology ; Tuberculosis - prevention & control ; Vaccination - veterinary</subject><ispartof>PLoS pathogens, 2009-04, Vol.5 (4), p.e1000392-e1000392</ispartof><rights>COPYRIGHT 2009 Public Library of Science</rights><rights>Chen et al. 2009</rights><rights>2009 Chen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Chen CY, Huang D, Wang RC, Shen L, Zeng G, et al. (2009) A Critical Role for CD8 T Cells in a Nonhuman Primate Model of Tuberculosis. 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Unlike mice, humans and nonhuman primates share a number of important features of the immune system that relate directly to the specificity and functions of CD8 T cells, such as the expression of group 1 CD1 proteins that are capable of presenting Mycobacterium tuberculosis lipids antigens and the cytotoxic/bactericidal protein granulysin. Employing a more relevant nonhuman primate model of human tuberculosis, we examined the contribution of BCG- or M. tuberculosis-elicited CD8 T cells to vaccine-induced immunity against tuberculosis. CD8 depletion compromised BCG vaccine-induced immune control of M. tuberculosis replication in the vaccinated rhesus macaques. Depletion of CD8 T cells in BCG-vaccinated rhesus macaques led to a significant decrease in the vaccine-induced immunity against tuberculosis. Consistently, depletion of CD8 T cells in rhesus macaques that had been previously infected with M. tuberculosis and cured by antibiotic therapy also resulted in a loss of anti-tuberculosis immunity upon M. tuberculosis re-infection. The current study demonstrates a major role for CD8 T cells in anti-tuberculosis immunity, and supports the view that CD8 T cells should be included in strategies for development of new tuberculosis vaccines and immunotherapeutics.</description><subject>Acquired immune deficiency syndrome</subject><subject>AIDS</subject><subject>Animals</subject><subject>BCG Vaccine - immunology</subject><subject>CD8 Antigens - immunology</subject><subject>CD8 lymphocytes</subject><subject>CD8-Positive T-Lymphocytes - immunology</subject><subject>Cytotoxicity</subject><subject>Disease Models, Animal</subject><subject>Genetic aspects</subject><subject>Health aspects</subject><subject>Human immunodeficiency virus</subject><subject>Humans</subject><subject>Immunology/Immunity to Infections</subject><subject>Infections</subject><subject>Infectious Diseases</subject><subject>Lymphocytes</subject><subject>Macaca mulatta</subject><subject>Multivariate analysis</subject><subject>Mycobacterium tuberculosis</subject><subject>Mycobacterium tuberculosis - immunology</subject><subject>Mycobacterium tuberculosis - physiology</subject><subject>Pathology</subject><subject>Prevention</subject><subject>Primates</subject><subject>Risk factors</subject><subject>Tuberculosis</subject><subject>Tuberculosis - immunology</subject><subject>Tuberculosis - prevention & control</subject><subject>Vaccination - veterinary</subject><issn>1553-7374</issn><issn>1553-7366</issn><issn>1553-7374</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>DOA</sourceid><recordid>eNqVkl2L1DAUhoso7rr6D0QDwoIXM-arSXMjDLN-DC4Kul6HND2ZzdA2s0kr-u9Nd6rugCCSi4ST57wn580piqcELwmT5NUujLE37XK_N8OSYIyZoveKU1KWbCGZ5PfvnE-KRyntMOaEEfGwOCGKVYQKfFp8WCEb_eCtaVEMLSAXIlpfVOgKWWjbhHyPDOpDfz12pkf76DszAOpCAy0KDg1jDdGObUg-PS4eONMmeDLvZ8XXt2-u1u8Xl5_ebdary4UVgg4LV9vaCkJrJVSDQTBMFTG2ZtAwYhXnFKRtHDNAGqDOSixKw5gSFQilcp9nxfOD7j6X1bMPSROqMJElpiwTmwPRBLPTt4-OP3QwXt8GQtxqE3PTLWgpseQlsJK4ilsOqqqoqEntLG2AkyZrvZ6rjXUHjYV-iKY9Ej2-6f213oZvmgrBKk6zwPksEMPNCGnQnU-TuaaHMCYtJCmnp_8TpLhUWMjJgBcHcGtyB753IRe2E6xXRKn8yYrwTC3_QuXVQOdt6MH5HD9KeHmUkJkBvg9bM6akN18-_wf78ZjlB9bGkFIE99s8gvU0y7_-UE-zrOdZzmnP7hr_J2keXvYTXEfuPQ</recordid><startdate>20090401</startdate><enddate>20090401</enddate><creator>Chen, Crystal Y</creator><creator>Huang, Dan</creator><creator>Wang, Richard C</creator><creator>Shen, Ling</creator><creator>Zeng, Gucheng</creator><creator>Yao, Shuyun</creator><creator>Shen, Yun</creator><creator>Halliday, Lisa</creator><creator>Fortman, Jeff</creator><creator>McAllister, Milton</creator><creator>Estep, Jim</creator><creator>Hunt, Robert</creator><creator>Vasconcelos, Daphne</creator><creator>Du, George</creator><creator>Porcelli, Steven A</creator><creator>Larsen, Michelle H</creator><creator>Jacobs, Jr, William R</creator><creator>Haynes, Barton F</creator><creator>Letvin, Norman L</creator><creator>Chen, Zheng W</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>ISN</scope><scope>ISR</scope><scope>7QL</scope><scope>7T5</scope><scope>7U9</scope><scope>C1K</scope><scope>H94</scope><scope>M7N</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20090401</creationdate><title>A critical role for CD8 T cells in a nonhuman primate model of tuberculosis</title><author>Chen, Crystal Y ; Huang, Dan ; Wang, Richard C ; Shen, Ling ; Zeng, Gucheng ; Yao, Shuyun ; Shen, Yun ; Halliday, Lisa ; Fortman, Jeff ; McAllister, Milton ; Estep, Jim ; Hunt, Robert ; Vasconcelos, Daphne ; Du, George ; Porcelli, Steven A ; Larsen, Michelle H ; Jacobs, Jr, William R ; Haynes, Barton F ; Letvin, Norman L ; Chen, Zheng W</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c662t-fbcbc612b969d0e630291acb3ed31c9442e7cdf3ae1de2fc7065a33968e699003</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Acquired immune deficiency syndrome</topic><topic>AIDS</topic><topic>Animals</topic><topic>BCG Vaccine - immunology</topic><topic>CD8 Antigens - immunology</topic><topic>CD8 lymphocytes</topic><topic>CD8-Positive T-Lymphocytes - immunology</topic><topic>Cytotoxicity</topic><topic>Disease Models, Animal</topic><topic>Genetic aspects</topic><topic>Health aspects</topic><topic>Human immunodeficiency virus</topic><topic>Humans</topic><topic>Immunology/Immunity to Infections</topic><topic>Infections</topic><topic>Infectious Diseases</topic><topic>Lymphocytes</topic><topic>Macaca mulatta</topic><topic>Multivariate analysis</topic><topic>Mycobacterium tuberculosis</topic><topic>Mycobacterium tuberculosis - immunology</topic><topic>Mycobacterium tuberculosis - physiology</topic><topic>Pathology</topic><topic>Prevention</topic><topic>Primates</topic><topic>Risk factors</topic><topic>Tuberculosis</topic><topic>Tuberculosis - immunology</topic><topic>Tuberculosis - prevention & control</topic><topic>Vaccination - veterinary</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Crystal Y</creatorcontrib><creatorcontrib>Huang, Dan</creatorcontrib><creatorcontrib>Wang, Richard C</creatorcontrib><creatorcontrib>Shen, Ling</creatorcontrib><creatorcontrib>Zeng, Gucheng</creatorcontrib><creatorcontrib>Yao, Shuyun</creatorcontrib><creatorcontrib>Shen, Yun</creatorcontrib><creatorcontrib>Halliday, Lisa</creatorcontrib><creatorcontrib>Fortman, Jeff</creatorcontrib><creatorcontrib>McAllister, Milton</creatorcontrib><creatorcontrib>Estep, Jim</creatorcontrib><creatorcontrib>Hunt, Robert</creatorcontrib><creatorcontrib>Vasconcelos, Daphne</creatorcontrib><creatorcontrib>Du, George</creatorcontrib><creatorcontrib>Porcelli, Steven A</creatorcontrib><creatorcontrib>Larsen, Michelle H</creatorcontrib><creatorcontrib>Jacobs, Jr, William R</creatorcontrib><creatorcontrib>Haynes, Barton F</creatorcontrib><creatorcontrib>Letvin, Norman L</creatorcontrib><creatorcontrib>Chen, Zheng W</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Canada</collection><collection>Gale In Context: Science</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Immunology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PLoS pathogens</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Crystal Y</au><au>Huang, Dan</au><au>Wang, Richard C</au><au>Shen, Ling</au><au>Zeng, Gucheng</au><au>Yao, Shuyun</au><au>Shen, Yun</au><au>Halliday, Lisa</au><au>Fortman, Jeff</au><au>McAllister, Milton</au><au>Estep, Jim</au><au>Hunt, Robert</au><au>Vasconcelos, Daphne</au><au>Du, George</au><au>Porcelli, Steven A</au><au>Larsen, Michelle H</au><au>Jacobs, Jr, William R</au><au>Haynes, Barton F</au><au>Letvin, Norman L</au><au>Chen, Zheng W</au><au>Bishai, William</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A critical role for CD8 T cells in a nonhuman primate model of tuberculosis</atitle><jtitle>PLoS pathogens</jtitle><addtitle>PLoS Pathog</addtitle><date>2009-04-01</date><risdate>2009</risdate><volume>5</volume><issue>4</issue><spage>e1000392</spage><epage>e1000392</epage><pages>e1000392-e1000392</pages><issn>1553-7374</issn><issn>1553-7366</issn><eissn>1553-7374</eissn><abstract>The role of CD8 T cells in anti-tuberculosis immunity in humans remains unknown, and studies of CD8 T cell-mediated protection against tuberculosis in mice have yielded controversial results. Unlike mice, humans and nonhuman primates share a number of important features of the immune system that relate directly to the specificity and functions of CD8 T cells, such as the expression of group 1 CD1 proteins that are capable of presenting Mycobacterium tuberculosis lipids antigens and the cytotoxic/bactericidal protein granulysin. Employing a more relevant nonhuman primate model of human tuberculosis, we examined the contribution of BCG- or M. tuberculosis-elicited CD8 T cells to vaccine-induced immunity against tuberculosis. CD8 depletion compromised BCG vaccine-induced immune control of M. tuberculosis replication in the vaccinated rhesus macaques. Depletion of CD8 T cells in BCG-vaccinated rhesus macaques led to a significant decrease in the vaccine-induced immunity against tuberculosis. Consistently, depletion of CD8 T cells in rhesus macaques that had been previously infected with M. tuberculosis and cured by antibiotic therapy also resulted in a loss of anti-tuberculosis immunity upon M. tuberculosis re-infection. The current study demonstrates a major role for CD8 T cells in anti-tuberculosis immunity, and supports the view that CD8 T cells should be included in strategies for development of new tuberculosis vaccines and immunotherapeutics.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>19381260</pmid><doi>10.1371/journal.ppat.1000392</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Acquired immune deficiency syndrome AIDS Animals BCG Vaccine - immunology CD8 Antigens - immunology CD8 lymphocytes CD8-Positive T-Lymphocytes - immunology Cytotoxicity Disease Models, Animal Genetic aspects Health aspects Human immunodeficiency virus Humans Immunology/Immunity to Infections Infections Infectious Diseases Lymphocytes Macaca mulatta Multivariate analysis Mycobacterium tuberculosis Mycobacterium tuberculosis - immunology Mycobacterium tuberculosis - physiology Pathology Prevention Primates Risk factors Tuberculosis Tuberculosis - immunology Tuberculosis - prevention & control Vaccination - veterinary |
| title | A critical role for CD8 T cells in a nonhuman primate model of tuberculosis |
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