{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:17:48Z","timestamp":1790727468301,"version":"4.1.0"},"reference-count":53,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2011,3,1]],"date-time":"2011-03-01T00:00:00Z","timestamp":1298937600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Understanding the early immunologic events accompanying reactivated tuberculosis (TB) in HIV-infected individuals may yield insight into causes of reactivation and improve treatment modalities. We used the cynomolgus macaque (Macaca fascicularis) model of HIV\u2013Mycobacterium tuberculosis coinfection to investigate the dynamics of multifunctional T cell responses and granuloma T cell phenotypes in reactivated TB. CD4+ and CD8+ T cells expressing Th1 cytokines (IFN-\u03b3, IL-2, TNF) and Th2 cytokines (IL-4 and IL-10) were followed from latent M. tuberculosis infection to reactivation after coinfection with a pathogenic SIV. Coinfected animals experienced increased Th1 cytokine responses to M. tuberculosis Ags above the latent-response baseline 3\u20135 wk post-SIV infection that corresponded with peak plasma viremia. Th2 cytokine expression was not Ag specific, but strong, transient IL-4 expression was noted 4\u20137 wk post-SIV infection. Animals reactivating &amp;lt;17 wk post-SIV infection had significantly more multifunctional CD4+ T cells 3\u20135 wk post-SIV infection and more Th2-polarized and fewer Th0-, Th1-polarized CD8+ T cells during weeks 1\u201310 post-SIV infection than animals reactivating &amp;gt;26 wk post-SIV infection. Granuloma T cells included Th0-, Th1-, and Th2-polarized phenotypes but were particularly rich in cytolytic (CD107+) T cells. When combined with the changes in peripheral blood T cells, these factors indicate that events during acute HIV infection are likely to include distortions in proinflammatory and anti-inflammatory T cell responses within the granuloma that have significant effects on reactivation of latent TB. Moreover, it appears that mycobacteria-specific multifunctional T cells are better correlates of Ag load (i.e., disease status) than of protection.<\/jats:p>","DOI":"10.4049\/jimmunol.1003773","type":"journal-article","created":{"date-parts":[[2011,2,12]],"date-time":"2011-02-12T05:01:49Z","timestamp":1297486909000},"page":"3527-3537","source":"Crossref","is-referenced-by-count":73,"title":["Simian Immunodeficiency Virus-Induced Changes in T Cell Cytokine Responses in Cynomolgus Macaques with Latent <i>Mycobacterium tuberculosis<\/i> Infection Are Associated with Timing of Reactivation"],"prefix":"10.1093","volume":"186","author":[{"given":"Joshua T","family":"Mattila","sequence":"first","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine , Pittsburgh, PA 15261"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Collin R","family":"Diedrich","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine , Pittsburgh, PA 15261"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philana Ling","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Children\u2019s Hospital of Pittsburgh of the University of Pittsburgh School of Medicine , Pittsburgh, PA 15224"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayao","family":"Phuah","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine , Pittsburgh, PA 15261"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JoAnne L","family":"Flynn","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine , Pittsburgh, PA 15261"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2011,3,15]]},"reference":[{"key":"2025032411155989000_r1","doi-asserted-by":"crossref","first-page":"1697","DOI":"10.1056\/NEJM199212103272401","article-title":"Clinical manifestations and predictors of disease progression in drug users with human immunodeficiency virus infection","volume":"327","author":"Selwyn","year":"1992","journal-title":"N. 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