{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T08:40:05Z","timestamp":1779093605194,"version":"3.51.4"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2000,2,1]],"date-time":"2000-02-01T00:00:00Z","timestamp":949363200000},"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":[[2000,2,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Recent studies indicate important roles for CTLA-4 engagement in T cells, and for TGF-\u03b2 production in the immunopathogenesis of murine kalaazar or visceral leishmaniasis, but a functional link between these two pathways in helping intracellular parasite growth is unknown. Here we report that Ag or anti-CD3 activation of splenic CD4+ T cells from visceral leishmaniasis leads to intense CTLA-4-mediated TGF-\u03b21 production, as assessed either by CTLA-4 blockade or by direct CTLA-4 cross-linkage. Production of TGF-\u03b21 accounted for the reciprocal regulation of IFN-\u03b3 production by CTLA-4 engagement. Following CD4+ T cell activation, intracellular growth of Leishmania chagasi in cocultured splenic macrophages required both CTLA-4 function and TGF-\u03b21 secretion. Cross-linkage of CTLA-4 markedly increased L. chagasi replication in cocultures of infected macrophages and activated CD4+ T cells, and parasite growth could be completely blocked with neutralizing anti-TGF-\u03b21 Ab. Exogenous addition of rTGF-\u03b21 restored parasite growth in cultures protected from parasitism by CTLA-4 blockade. These results indicate that the negative costimulatory receptor CTLA-4 is critically involved in TGF-\u03b2 production and in intracellular parasite replication seen in murine kalaazar.<\/jats:p>","DOI":"10.4049\/jimmunol.164.4.2001","type":"journal-article","created":{"date-parts":[[2014,4,22]],"date-time":"2014-04-22T14:44:52Z","timestamp":1398177892000},"page":"2001-2008","source":"Crossref","is-referenced-by-count":78,"title":["TGF-\u03b2 Mediates CTLA-4 Suppression of Cellular Immunity in Murine Kalaazar"],"prefix":"10.1093","volume":"164","author":[{"given":"Nitza A","family":"Gomes","sequence":"first","affiliation":[{"name":"Immunobiology Program, Instituto de Biofi\u0301sica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro , Rio de Janeiro ,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cerli R","family":"Gattass","sequence":"additional","affiliation":[{"name":"Immunobiology Program, Instituto de Biofi\u0301sica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro , Rio de Janeiro ,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victor","family":"Barreto-de-Souza","sequence":"additional","affiliation":[{"name":"Immunobiology Program, Instituto de Biofi\u0301sica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro , Rio de Janeiro ,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary E","family":"Wilson","sequence":"additional","affiliation":[{"name":"Departments of Internal Medicine and Microbiology, University of Iowa , Iowa City, IA 52242"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George A","family":"DosReis","sequence":"additional","affiliation":[{"name":"Immunobiology Program, Instituto de Biofi\u0301sica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro , Rio de Janeiro ,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2000,2,15]]},"reference":[{"key":"2026020213175980900_R1","first-page":"155","volume-title":"Immunol. 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