{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T08:08:00Z","timestamp":1791446880273,"version":"4.3.3"},"reference-count":40,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[1995,8]]},"abstract":"<jats:p>\n                    <jats:italic>Background<\/jats:italic>\n                    \u03b2-Hemolytic streptococcal infection in developing countries still causes thousands of cases of rheumatic heart disease, demanding surgical valve correction. Antigenic mimicry between self and streptococcal components has been proposed as the triggering factor leading to autoimmunity in individuals with genetic susceptibility. Although heart streptococcal\u2013M protein cross-reactive antibodies have been demonstrated, heart tissue damage seems to be T lymphocyte\u2013dependent. We studied the infiltrating T lymphocytes in rheumatic heart lesions with the aim of understanding the role of cellular immune response at the site of the lesions.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:italic>Methods and Results<\/jats:italic>\n                    We obtained 107 T-cell clones from surgical fragments of cardiac tissue from four rheumatic heart disease patients. We tested their capacity to recognize streptococcal M protein\u2013derived synthetic peptides and heart proteins. We found eight infiltrating T-cell clones from all four patients that simultaneously recognize streptococcal M and heart proteins. Among the M-protein sequences tested, only synthetic peptides corresponding to regions 1 through 25, 81 through 103, and 163 through 177 were simultaneously recognized with heart protein fractions. Interestingly, regions 81 through 103 and 163 through 177 have been known to bear heart cross-reactive epitopes at the antibody level. Five of these clones are CD4\n                    <jats:sup>+<\/jats:sup>\n                    , and one is CD8\n                    <jats:sup>+<\/jats:sup>\n                    .\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:italic>Conclusions<\/jats:italic>\n                    The presence of heart\u2013M protein cross-reactive T-cell clones in rheumatic heart lesions suggests their direct involvement in the pathogenesis of this disease. The dissection of protective and pathogenic epitopes of streptococcal M protein is an important step in allowing the development of a safe anti-streptococcal synthetic vaccine.\n                  <\/jats:p>","DOI":"10.1161\/01.cir.92.3.415","type":"journal-article","created":{"date-parts":[[2012,6,11]],"date-time":"2012-06-11T20:34:42Z","timestamp":1339446882000},"page":"415-420","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":155,"title":["Human Heart\u2013Infiltrating T-Cell Clones From Rheumatic Heart Disease Patients Recognize Both Streptococcal and Cardiac Proteins"],"prefix":"10.1161","volume":"92","author":[{"given":"L.","family":"Guilherme","sequence":"first","affiliation":[{"name":"From the Instituto do Corac\u0327a\u0303o do Hospital das Clinicas, Faculdade de Medicina da Universidade de Sa\u0303o Paulo (Brazil), and the Instituto de Immunologia, Hospital San Juan de Dios, Universidad Nacional de Colombia, Bogota, Colombia (M.E.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Cunha-Neto","sequence":"additional","affiliation":[{"name":"From the Instituto do Corac\u0327a\u0303o do Hospital das Clinicas, Faculdade de Medicina da Universidade de Sa\u0303o Paulo (Brazil), and the Instituto de Immunologia, Hospital San Juan de Dios, Universidad Nacional de Colombia, Bogota, Colombia (M.E.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V.","family":"Coelho","sequence":"additional","affiliation":[{"name":"From the Instituto do Corac\u0327a\u0303o do Hospital das Clinicas, Faculdade de Medicina da Universidade de Sa\u0303o Paulo (Brazil), and the Instituto de Immunologia, Hospital San Juan de Dios, Universidad Nacional de Colombia, Bogota, Colombia (M.E.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Snitcowsky","sequence":"additional","affiliation":[{"name":"From the Instituto do Corac\u0327a\u0303o do Hospital das Clinicas, Faculdade de Medicina da Universidade de Sa\u0303o Paulo (Brazil), and the Instituto de Immunologia, Hospital San Juan de Dios, Universidad Nacional de Colombia, Bogota, Colombia (M.E.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. M. A.","family":"Pomerantzeff","sequence":"additional","affiliation":[{"name":"From the Instituto do Corac\u0327a\u0303o do Hospital das Clinicas, Faculdade de Medicina da Universidade de Sa\u0303o Paulo (Brazil), and the Instituto de Immunologia, Hospital San Juan de Dios, Universidad Nacional de Colombia, Bogota, Colombia (M.E.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. V.","family":"Assis","sequence":"additional","affiliation":[{"name":"From the Instituto do Corac\u0327a\u0303o do Hospital das Clinicas, Faculdade de Medicina da Universidade de Sa\u0303o Paulo (Brazil), and the Instituto de Immunologia, Hospital San Juan de Dios, Universidad Nacional de Colombia, Bogota, Colombia (M.E.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Pedra","sequence":"additional","affiliation":[{"name":"From the Instituto do Corac\u0327a\u0303o do Hospital das Clinicas, Faculdade de Medicina da Universidade de Sa\u0303o Paulo (Brazil), and the Instituto de Immunologia, Hospital San Juan de Dios, Universidad Nacional de Colombia, Bogota, Colombia (M.E.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Neumann","sequence":"additional","affiliation":[{"name":"From the Instituto do Corac\u0327a\u0303o do Hospital das Clinicas, Faculdade de Medicina da Universidade de Sa\u0303o Paulo (Brazil), and the Instituto de Immunologia, Hospital San Juan de Dios, Universidad Nacional de Colombia, Bogota, Colombia (M.E.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Goldberg","sequence":"additional","affiliation":[{"name":"From the Instituto do Corac\u0327a\u0303o do Hospital das Clinicas, Faculdade de Medicina da Universidade de Sa\u0303o Paulo (Brazil), and the Instituto de Immunologia, Hospital San Juan de Dios, Universidad Nacional de Colombia, Bogota, Colombia (M.E.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. E.","family":"Patarroyo","sequence":"additional","affiliation":[{"name":"From the Instituto do Corac\u0327a\u0303o do Hospital das Clinicas, Faculdade de Medicina da Universidade de Sa\u0303o Paulo (Brazil), and the Instituto de Immunologia, Hospital San Juan de Dios, Universidad Nacional de Colombia, Bogota, Colombia (M.E.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Pileggi","sequence":"additional","affiliation":[{"name":"From the Instituto do Corac\u0327a\u0303o do Hospital das Clinicas, Faculdade de Medicina da Universidade de Sa\u0303o Paulo (Brazil), and the Instituto de Immunologia, Hospital San Juan de Dios, Universidad Nacional de Colombia, Bogota, Colombia (M.E.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Kalil","sequence":"additional","affiliation":[{"name":"From the Instituto do Corac\u0327a\u0303o do Hospital das Clinicas, Faculdade de Medicina da Universidade de Sa\u0303o Paulo (Brazil), and the Instituto de Immunologia, Hospital San Juan de Dios, Universidad Nacional de Colombia, Bogota, Colombia (M.E.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0090-1229(05)80019-4"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.156.4.1165"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.162.2.583"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.142.7.2475"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0167-5699(92)90173-5"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(83)91124-5"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/0090-1229(89)90174-8"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.126.4.1499"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.142.3.966"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.172.1.359"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.60.2.701-705.1992"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.152.4.2066"},{"key":"e_1_3_2_13_2","first-page":"818","volume":"64","year":"1986","unstructured":"Mackenzie WA, Scharts AE, Friedman EW, Davies TF. Intrathyroidal T cell clones from patients with autoimmune thyroid disease. J Clin Endocrinol Metab. 1986;64:818-824.","journal-title":"J Clin Endocrinol Metab"},{"key":"e_1_3_2_14_2","first-page":"273","volume":"11","year":"1989","unstructured":"Quaile A, Kejeldsen-kragh J, Forre O, Waalen K, Sioud M, Kafvenes C, Natvig JB. Immunoregulatory T cell activation in rheumatoid arthritis: a need for analysis on the clonal and molecular level. Springer Semin Immunopathol. 1989;11:273-287.","journal-title":"Springer Semin Immunopathol"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.1990.tb05182.x"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI111774"},{"key":"e_1_3_2_17_2","first-page":"233","volume":"8","year":"1989","unstructured":"Weber T, Kaufman C, Zeevi A, Zerbi TR, Hardesty RJ, Kormos RH, Griffith BP, Duquesnoy RJ. Lymphocyte growth from cardiac allograft biopsy specimens with no or minimal cellular infiltrates: association with subsequent rejection episode. Heart Transplant. 1989;8:233-240.","journal-title":"Heart Transplant"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)43150-4"},{"key":"e_1_3_2_19_2","doi-asserted-by":"crossref","unstructured":"Phillips GN Jr Flicker PF Cohen C Manjula BN Fischetti VA. Streptococcal M protein: alpha-helical coiled-coil structure and arrangement on the cell surface. Proc Natl Acad Sci U S A. 1981;78: 4689-4693.","DOI":"10.1073\/pnas.78.8.4689"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.82.15.5131"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3024.1992.tb00010.x"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-1759(87)90429-7"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/332158a0"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199109123251106"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI107780"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.163.5.1191"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.143.8.2677"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.59.12.4324-4331.1991"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.1991.tb00825.x"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.82.4.1064"},{"key":"e_1_3_2_31_2","first-page":"285","volume":"138","year":"1991","unstructured":"Gulizia JM, Cunningham MW, McManus BM. Immunoreactivity of anti-streptococcal monoclonal antibodies to human heart valves: evidence for multiple cross-reactive epitopes. Am J Pathol. 1991;138:285-301.","journal-title":"Am J Pathol"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI112531"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-8703(86)90311-X"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0039.1986.tb01517.x"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1136\/hrt.58.6.659"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.76.2.3475188"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.83.6.2040052"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/0198-8859(94)90024-8"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.147.8.2663"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.178.1.27"}],"container-title":["Circulation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/01.CIR.92.3.415","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T11:48:32Z","timestamp":1715514512000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/01.CIR.92.3.415"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1995,8]]},"references-count":40,"journal-issue":{"issue":"3","published-print":{"date-parts":[[1995,8]]}},"alternative-id":["10.1161\/01.CIR.92.3.415"],"URL":"https:\/\/doi.org\/10.1161\/01.cir.92.3.415","relation":{},"ISSN":["0009-7322","1524-4539"],"issn-type":[{"value":"0009-7322","type":"print"},{"value":"1524-4539","type":"electronic"}],"subject":[],"published":{"date-parts":[[1995,8]]},"assertion":[{"value":"1994-09-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"1995-01-19","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"1995-08-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}