Detection of Polyfunctional Mycobacterium tuberculosis–Specific T Cells and Association with Viral Load in HIV-1–Infected Persons
Identifieur interne : 002A36 ( Main/Exploration ); précédent : 002A35; suivant : 002A37Detection of Polyfunctional Mycobacterium tuberculosis–Specific T Cells and Association with Viral Load in HIV-1–Infected Persons
Auteurs : Cheryl L. Day [Afrique du Sud, États-Unis] ; Nompumelelo Mkhwanazi [Afrique du Sud] ; Sharon Reddy [Afrique du Sud] ; Zenele Mncube [Afrique du Sud] ; Mary Van Der Stok [Afrique du Sud] ; Paul Klenerman [Royaume-Uni] ; Bruce D. Walker [Afrique du Sud, États-Unis]Source :
- The Journal of Infectious Diseases [ 0022-1899 ] ; 2008.
Abstract
BackgroundThe human immunodeficiency virus type 1 (HIV-1) epidemic is associated with a significant increase in the incidence of tuberculosis (TB); however, little is known about the quality of Mycobacterium tuberculosis (MTB)–specific cellular immune responses in coinfected individuals MethodsA total of 137 HIV-1–positive individuals in Durban, South Africa, were screened with the use of overlapping peptides spanning Ag85A, culture filtrate protein 10 (CFP-10), early secretory antigen target 6 (ESAT-6), and TB10.4, in an interferon (IFN)–γ enzyme-linked immunospot (ELISPOT) assay. Intracellular cytokine staining for MTB-specific production of IFN-γ, tumor necrosis factor (TNF)–α, and interleukin (IL)–2 was performed, as was ex vivo phenotyping of memory markers on MTB-specific T cells ResultsA total of 41% of subjects responded to ESAT-6 and/or CFP-10, indicating the presence of latent MTB infection. The proportion of MTB-specific IFN-γ+/TNF-α+ CD4+ cells was significantly higher than the proportion of IFN-γ+/IL-2+ CD4+ cells (P=.0220), and the proportion of MTB-specific IL-2–secreting CD4 cells was inversely correlated with the HIV-1 load (P=.0098). MTB-specific CD8 T cells were predominately IFN-γ+/TNF-α+/IL-2−. Ex vivo memory phenotyping of MTB-specific CD4 and CD8 T cells indicated an early to intermediate differentiated phenotype for the population of effector memory cells ConclusionsPolyfunctional MTB-specific CD4 and CD8 T cell responses are maintained in the peripheral blood of HIV-1–positive individuals, in the absence of active disease, and the functional capacity of these responses is affected by HIV-1 disease status
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DOI: 10.1086/529048
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Walker</name></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:76EEEEF00CA41E97ECFBE108945D1CF993979DD1</idno><date when="2008" year="2008">2008</date><idno type="doi">10.1086/529048</idno><idno type="url">https://api.istex.fr/ark:/67375/HXZ-XWB4MNG9-1/fulltext.pdf</idno><idno type="wicri:Area/Istex/Corpus">001D45</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">001D45</idno><idno type="wicri:Area/Istex/Curation">001D45</idno><idno type="wicri:Area/Istex/Checkpoint">000750</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Checkpoint">000750</idno><idno type="wicri:doubleKey">0022-1899:2008:Day C:detection:of:polyfunctional</idno><idno type="wicri:Area/Main/Merge">002A62</idno><idno type="wicri:Area/Main/Curation">002A36</idno><idno type="wicri:Area/Main/Exploration">002A36</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main">Detection of Polyfunctional <hi rend="italic">Mycobacterium tuberculosis</hi>–Specific T Cells and Association with Viral Load in HIV-1–Infected Persons</title><author wicri:is="90%"><name sortKey="Day, Cheryl L" sort="Day, Cheryl L" uniqKey="Day C" first="Cheryl L" last="Day">Cheryl L. Day</name><affiliation wicri:level="1"><country xml:lang="fr">Afrique du Sud</country><wicri:regionArea>HIV Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu NatalDurban</wicri:regionArea><wicri:noRegion>University of KwaZulu NatalDurban</wicri:noRegion></affiliation><affiliation></affiliation><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>Division of AIDS, Harvard Medical SchoolBoston</wicri:cityArea></affiliation><affiliation wicri:level="1"><country wicri:rule="url">Afrique du Sud</country></affiliation><affiliation wicri:level="1"><country wicri:rule="url">Afrique du Sud</country><wicri:regionArea>Reprints or correspondence: Dr. Cheryl L. Day, South African Tuberculosis Vaccine Initiative, Institute for Infectious Diseases and Molecular Medicine, University of Cape Town, S1.02 Wernher and Beit Bldg., Anzio Rd., Observatory 7925, Cape Town</wicri:regionArea><wicri:noRegion>Cape Town</wicri:noRegion></affiliation></author><author wicri:is="90%"><name sortKey="Mkhwanazi, Nompumelelo" sort="Mkhwanazi, Nompumelelo" uniqKey="Mkhwanazi N" first="Nompumelelo" last="Mkhwanazi">Nompumelelo Mkhwanazi</name><affiliation wicri:level="1"><country xml:lang="fr">Afrique du Sud</country><wicri:regionArea>HIV Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu NatalDurban</wicri:regionArea><wicri:noRegion>University of KwaZulu NatalDurban</wicri:noRegion></affiliation></author><author wicri:is="90%"><name sortKey="Reddy, Sharon" sort="Reddy, Sharon" uniqKey="Reddy S" first="Sharon" last="Reddy">Sharon Reddy</name><affiliation wicri:level="1"><country xml:lang="fr">Afrique du Sud</country><wicri:regionArea>HIV Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu NatalDurban</wicri:regionArea><wicri:noRegion>University of KwaZulu NatalDurban</wicri:noRegion></affiliation></author><author wicri:is="90%"><name sortKey="Mncube, Zenele" sort="Mncube, Zenele" uniqKey="Mncube Z" first="Zenele" last="Mncube">Zenele Mncube</name><affiliation wicri:level="1"><country xml:lang="fr">Afrique du Sud</country><wicri:regionArea>HIV Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu NatalDurban</wicri:regionArea><wicri:noRegion>University of KwaZulu NatalDurban</wicri:noRegion></affiliation></author><author wicri:is="90%"><name sortKey="Van Der Stok, Mary" sort="Van Der Stok, Mary" uniqKey="Van Der Stok M" first="Mary" last="Van Der Stok">Mary Van Der Stok</name><affiliation wicri:level="1"><country xml:lang="fr">Afrique du Sud</country><wicri:regionArea>HIV Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu NatalDurban</wicri:regionArea><wicri:noRegion>University of KwaZulu NatalDurban</wicri:noRegion></affiliation></author><author wicri:is="90%"><name sortKey="Klenerman, Paul" sort="Klenerman, Paul" uniqKey="Klenerman P" first="Paul" last="Klenerman">Paul Klenerman</name><affiliation wicri:level="1"><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Nuffield Department of Medicine, The Peter Medawar Building for Pathogen Research, Oxford UniversityOxford</wicri:regionArea><wicri:noRegion>Oxford UniversityOxford</wicri:noRegion></affiliation></author><author wicri:is="90%"><name sortKey="Walker, Bruce D" sort="Walker, Bruce D" uniqKey="Walker B" first="Bruce D" last="Walker">Bruce D. 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Intracellular cytokine staining for MTB-specific production of IFN-γ, tumor necrosis factor (TNF)–α, and interleukin (IL)–2 was performed, as was ex vivo phenotyping of memory markers on MTB-specific T cells ResultsA total of 41% of subjects responded to ESAT-6 and/or CFP-10, indicating the presence of latent MTB infection. The proportion of MTB-specific IFN-γ+/TNF-α+ CD4+ cells was significantly higher than the proportion of IFN-γ+/IL-2+ CD4+ cells (P=.0220), and the proportion of MTB-specific IL-2–secreting CD4 cells was inversely correlated with the HIV-1 load (P=.0098). MTB-specific CD8 T cells were predominately IFN-γ+/TNF-α+/IL-2−. Ex vivo memory phenotyping of MTB-specific CD4 and CD8 T cells indicated an early to intermediate differentiated phenotype for the population of effector memory cells ConclusionsPolyfunctional MTB-specific CD4 and CD8 T cell responses are maintained in the peripheral blood of HIV-1–positive individuals, in the absence of active disease, and the functional capacity of these responses is affected by HIV-1 disease status</div></front></TEI><affiliations><list><country><li>Afrique du Sud</li><li>Royaume-Uni</li><li>États-Unis</li></country><region><li>Maryland</li><li>Massachusetts</li></region></list><tree><country name="Afrique du Sud"><noRegion><name sortKey="Day, Cheryl L" sort="Day, Cheryl L" uniqKey="Day C" first="Cheryl L" last="Day">Cheryl L. Day</name></noRegion><name sortKey="Day, Cheryl L" sort="Day, Cheryl L" uniqKey="Day C" first="Cheryl L" last="Day">Cheryl L. Day</name><name sortKey="Day, Cheryl L" sort="Day, Cheryl L" uniqKey="Day C" first="Cheryl L" last="Day">Cheryl L. Day</name><name sortKey="Mkhwanazi, Nompumelelo" sort="Mkhwanazi, Nompumelelo" uniqKey="Mkhwanazi N" first="Nompumelelo" last="Mkhwanazi">Nompumelelo Mkhwanazi</name><name sortKey="Mncube, Zenele" sort="Mncube, Zenele" uniqKey="Mncube Z" first="Zenele" last="Mncube">Zenele Mncube</name><name sortKey="Reddy, Sharon" sort="Reddy, Sharon" uniqKey="Reddy S" first="Sharon" last="Reddy">Sharon Reddy</name><name sortKey="Van Der Stok, Mary" sort="Van Der Stok, Mary" uniqKey="Van Der Stok M" first="Mary" last="Van Der Stok">Mary Van Der Stok</name><name sortKey="Walker, Bruce D" sort="Walker, Bruce D" uniqKey="Walker B" first="Bruce D" last="Walker">Bruce D. Walker</name></country><country name="États-Unis"><region name="Massachusetts"><name sortKey="Day, Cheryl L" sort="Day, Cheryl L" uniqKey="Day C" first="Cheryl L" last="Day">Cheryl L. Day</name></region><name sortKey="Walker, Bruce D" sort="Walker, Bruce D" uniqKey="Walker B" first="Bruce D" last="Walker">Bruce D. Walker</name><name sortKey="Walker, Bruce D" sort="Walker, Bruce D" uniqKey="Walker B" first="Bruce D" last="Walker">Bruce D. Walker</name></country><country name="Royaume-Uni"><noRegion><name sortKey="Klenerman, Paul" sort="Klenerman, Paul" uniqKey="Klenerman P" first="Paul" last="Klenerman">Paul Klenerman</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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