{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T02:46:15Z","timestamp":1791081975041,"version":"4.1.0"},"reference-count":22,"publisher":"BMJ","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gut"],"published-print":{"date-parts":[[1993,2]]},"abstract":"<jats:p>Numbers of T cell receptor (TcR) gamma delta+ and alpha beta+ intestinal lymphocytes were studied in 34 coeliac patients in respect of their diet and the grade of villous atrophy. Particular attention was given to a group of 21 patients with coeliac disease according to ESPGAN criteria who were on a well tolerated long term normal diet and in nine of whom the mucosa had returned to normal or nearly normal. A significant increase in TcR gamma delta+ cells was observed in the gut epithelium of coeliac patients compared with age matched controls, and this did not correlate with either the presence of gluten in the diet or with the grade of villous atrophy. Thus, numbers of TcR gamma delta+ intraepithelial lymphocytes (IEL) were considerably above the normal range in four of seven patients on a gluten free diet and in four of nine patients who had recovered a normal or nearly normal mucosa in spite of a normal diet. In contrast, numbers of intestinal TcR alpha beta+ cells varied with the stage of the disease. Their number was high in the epithelium of patients with active coeliac disease (n = 18) but significantly less in patients whose mucosa had returned to normal or nearly normal either after gluten free diet (n = 7) or in spite of a normal diet (n = 9). Immunohistochemical markers of intestinal mononuclear cell activation detected in active coeliac disease were either weakly expressed or absent in the latter patients. It is suggested that TcR alpha beta+ but not TcR gamma delta+ IEL are sensitised to gliadin in coeliac disease, and that only the former cells play a direct part in the pathogenesis of the villous atrophy. The normal counts of TcR alpha beta+ IEL and the absence of detectable mononuclear activation in the biopsy specimens of a few patients who have recovered clinical and histological tolerance to gluten sustains this hypothesis and also suggests that immunological tolerance to gluten may be acquired in a subgroup of coeliac patients. Hte appreciable increase in TcR gamma delta+ IEL observed in some of the latter patients, however, is similar to that observed in latent coeliac disease urging for their careful and prolonged follow up until the role of TcR gamma delta+ IEL in the pathogenesis of coeliac disease is elucidated.<\/jats:p>","DOI":"10.1136\/gut.34.2.208","type":"journal-article","created":{"date-parts":[[2007,9,18]],"date-time":"2007-09-18T17:41:31Z","timestamp":1190137291000},"page":"208-214","source":"Crossref","is-referenced-by-count":153,"title":["Numbers of T cell receptor (TCR) alpha beta+ but not of TcR gamma delta+ intraepithelial lymphocytes correlate with the grade of villous atrophy in coeliac patients on a long term normal diet."],"prefix":"10.1136","volume":"34","author":[{"given":"T","family":"Kutlu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N","family":"Brousse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Rambaud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F","family":"Le Deist","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Schmitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N","family":"Cerf-Bensussan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[1993,2,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1084\/jem.167.4.1341","article-title":"Evidence that activated mucosal T cells play a role in the pathogenesis of enteropathy in human small intestine","volume":"167","author":"McDonald, T.T.; Spencer, J.","year":"1988","unstructured":"McDonald TT, Spencer J. Evidence that activated mucosal T cells play a role in the pathogenesis of enteropathy in human small intestine. ] Exp Med 1988; 167: 1341-9.","journal-title":"Exp Med"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"509","DOI":"10.3109\/08820138909112260","article-title":"The immunopathology of the small intestinal reaction in gluten-sensitivity","volume":"167","author":"Marsh, M.N.","year":"1989","unstructured":"Marsh MN. The immunopathology of the small intestinal reaction in gluten-sensitivity. Immunol Invest 1989; 167: 509-3 1.","journal-title":"Immunol Invest"},{"key":"ref_3","first-page":"781","article-title":"Lymphocyte activation by gliadin in coeliac disease and in experimentally induced enteropathy of germ-free rats","volume-title":"Advances in immunology","author":"Tlaskalova-Hogenova, H.; Stepankova, R.; Fric, P.; Kolinska, J.; Vancikova, Z.; Jileck, M.","year":"1990","unstructured":"Tlaskalova-Hogenova H, Stepankova R, Fric P, Kolinska J, Vancikova Z, Jileck M, et al. Lymphocyte activation by gliadin in coeliac disease and in experimentally induced enteropathy of germ-free rats. In: McDonald TT, ed. Advances in immunology. Lancaster; Kluwer Academic Publishers, 1990: 781-4."},{"key":"ref_4","first-page":"1335","article-title":"Expression of disulfide-linked and non-disulfide-linked forms of the T cell receptor y\/6 heterodimer in human intraepithelial lymphocytes","volume":"19","author":"Spencer, J.; Isaacson, P.G.; Diss, T.C.; McDonald, T.T.","year":"1989","unstructured":"Spencer J, Isaacson PG, Diss TC, McDonald TT. Expression of disulfide-linked and non-disulfide-linked forms of the T cell receptor y\/6 heterodimer in human intraepithelial lymphocytes. Eur]7 Immunol 1989; 19: 1335-8."},{"key":"ref_5","first-page":"665","article-title":"Intrapithelial T cells of the TcR y\/b + CD8-and V6l1\/Jb1+ phenotypes are increased in celiac disease. Scand j Immunol","volume":"30","author":"Halstensen, T.S.; Scott, H.; Brantzaeg, P.","year":"1989","unstructured":"Halstensen TS, Scott H, Brantzaeg P. Intrapithelial T cells of the TcR y\/b + CD8-and V6l1\/Jb1+ phenotypes are increased in celiac disease. Scand j Immunol, 1989; 30: 665-72."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1203\/00006450-199012000-00005","article-title":"Intestinal gamma\/delta receptor bearing T lymphocytes in celiac disease and inflammatory bowel diseases in children. Constant increase in celiac disease","volume":"28","author":"Savilahti, E.; Arato, A.; Verkasalo, M.","year":"1990","unstructured":"Savilahti E, Arato A, Verkasalo M. Intestinal gamma\/delta receptor bearing T lymphocytes in celiac disease and inflammatory bowel diseases in children. Constant increase in celiac disease. Pediatr Res 1990; 28: 579-81.","journal-title":"Pediatr Res"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1111\/j.1600-065X.1991.tb00591.x","article-title":"Biology of the human y(6 T-cell receptor","volume":"120","author":"Porcelli, S.; Brenner, M.B.; Band, H.","year":"1991","unstructured":"Porcelli S, Brenner MB, Band H. Biology of the human y(6 T-cell receptor. Immunol Rev 1991; 120: 137-83.","journal-title":"Immunol Rev"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1084\/jem.173.2.471","article-title":"Two gut intraepithelial CD8+ lymphocyte populations with different T cell receptors: a role for the gut epithelium in T-cell differentiation","volume":"173","author":"Guy-Grand, D.; Cerf-Bensussan, N.; Malissen, B.; Malassis-Seris, M.; Briottet, C.; Vassalli, P.","year":"1991","unstructured":"Guy-Grand D, Cerf-Bensussan N, Malissen B, Malassis-Seris M, Briottet C, Vassalli P. Two gut intraepithelial CD8+ lymphocyte populations with different T cell receptors: a role for the gut epithelium in T-cell differentiation. J Exp Med 1991; 173: 471-81.","journal-title":"J Exp Med"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1016\/0016-5085(90)90624-A","article-title":"Classification of intractable diarrhea in infancy using clinical and immunohistological criteria","volume":"99","author":"true","year":"1990","unstructured":"Cuenod B, Brousse N, Goulet 0, De Potter S, Mougenot J-F, Ricour C, et al. Classification of intractable diarrhea in infancy using clinical and immunohistological criteria. Gastroenterology 1990; 99: 1037-43.","journal-title":"Gastroenterology"},{"key":"ref_10","first-page":"259","article-title":"Transient mucosal atrophy in confirmed coeliac disease","author":"Schmitz, J.; Jos, J.; Rey, J.","year":"1978","unstructured":"Schmitz J,Jos J,Rey J. Transient mucosal atrophy in confirmed coeliac disease. In: McNicholl B, McCarth CF, Fottrell PF, eds. Lancaster: MTP Press, 1978: 259-66."},{"key":"ref_11","first-page":"1054","article-title":"Long term follow-up of childhood coeliac disease. Is there a natural recovery?","volume":"18","author":"Schmitz, J.; Arnaud-Battandier, F.; Jos, J.; Rey, J.","year":"1984","unstructured":"Schmitz J, Arnaud-Battandier F, Jos J, Rey J. Long term follow-up of childhood coeliac disease. Is there a natural recovery? Pediatr Res 1984; 18: 1054 [Abstract].","journal-title":"Pediatr Res"},{"key":"ref_12","first-page":"565","article-title":"Childhood celiac disease: a longterm analysis of relapses in 91 patients","volume":"5","author":"Shmerling, D.H.; Franckx, J.","year":"1986","unstructured":"Shmerling DH, Franckx J. Childhood celiac disease: a longterm analysis of relapses in 91 patients. J Pediatr Gastroenterol Nutr 1986; 5: 565-9.","journal-title":"J Pediatr Gastroenterol Nutr"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1604","DOI":"10.1136\/adc.64.11.1604","article-title":"Postpubertal gluten challenge in coeliac disease","volume":"64","year":"1989","unstructured":"Maki M, Lahdeaho ML, Hallstrom 0, Viander M, Visakorpi JK. Postpubertal gluten challenge in coeliac disease. Arch Dis Child 1989; 64: 1604-7.","journal-title":"Arch Dis Child"},{"key":"ref_14","first-page":"461","article-title":"Round table discussion. Diagnosis criteria in coeliac disease","volume":"59","author":"Weijers, H.A.; Lindquist, B.; Anderson, C.M.; Rev, J.; Shmerling, D.H.; Visakorpi, J.K.","year":"1970","unstructured":"Weijers HA,Lindquist B, Anderson CM, Rev J, Shmerling DH, Visakorpi JK, et al. Round table discussion. Diagnosis criteria in coeliac disease. Acta Paediatr Scand 1970; 59: 461-3.","journal-title":"Acta Paediatr Scand"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1136\/adc.65.8.909","article-title":"Revised criteria for diagnosis of coeliac disease","volume":"65","author":"Walker-Smith, J.A.; Gandalini, S.; Schmitz, J.; Shmerling, D.H.; Visakorpi, J.K.","year":"1990","unstructured":"Walker-Smith JA, Gandalini S, Schmitz J, Shmerling DH, Visakorpi JK. Revised criteria for diagnosis of coeliac disease. Arch Dis Child 1990; 65: 909-11.","journal-title":"Arch Dis Child"},{"key":"ref_16","first-page":"2615","article-title":"Immunohistologic and immunoelectron microscopic characterization of the mucosal lymphocytes of human small intestine by the use of monoclonal antibodies..7 Immunol","volume":"130","author":"Cerf-Bensussan, N.; Schneeberger, E.E.; Bhan, A.K.","year":"1983","unstructured":"Cerf-Bensussan N, Schneeberger EE, Bhan AK. Immunohistologic and immunoelectron microscopic characterization of the mucosal lymphocytes of human small intestine by the use of monoclonal antibodies..7 Immunol 1983; 130: 2615-22."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1632","DOI":"10.1136\/gut.29.12.1632","article-title":"Same peculiar subset of HML-1 + lymphocytes present in the normal intestinal epithelium is associated with tumoral epithelium of gastrointestinal carcinomas","volume":"29","author":"Jarry, A.; Cerf-Bensussan, N.; Brousse, N.; Guy-Grand, D.; Muzeau, F.; Potet, F.","year":"1988","unstructured":"Jarry A, Cerf-Bensussan N,Brousse N, Guy-Grand D, Muzeau F, Potet F. Same peculiar subset of HML-1 + lymphocytes present in the normal intestinal epithelium is associated with tumoral epithelium of gastrointestinal carcinomas. Gut 1988; 29: 1632-8.","journal-title":"Gut"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/0092-8674(90)90166-C","article-title":"Goodman 'l'. Extrathymic selection of TcR yo+ T cells by class II major histocompatibility complex molecules","volume":"63","author":"Lefrancois, L.; Lecorre, R.; Mayo, J.; Bluestone, J.A.","year":"1990","unstructured":"Lefrancois L, Lecorre R, Mayo J, Bluestone JA, Goodman 'l'. Extrathymic selection of TcR yo+ T cells by class II major histocompatibility complex molecules. Cell 1990; 63: 333-40.","journal-title":"Cell"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1500","DOI":"10.1016\/0140-6736(92)91262-7","article-title":"Intraepithelial yo T-cell receptor lymphocytes and genetic susceptibility to cGeliac disease","volume":"339","author":"Holm, K.; Maki, M.; Savilahti, E.; Lipsanen, V.; Laippala, P.; Koskimies, S.","year":"1992","unstructured":"Holm K, Maki M, Savilahti E, Lipsanen V, Laippala P, Koskimies S. Intraepithelial yo T-cell receptor lymphocytes and genetic susceptibility to cGeliac disease. Lancet 1992; 339: 1500-3.","journal-title":"Lancet"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/0167-5699(90)90015-2","article-title":"Recognition of heat-shock-proteins and yo T cell function","volume":"11","author":"Born, W.; Happ, M.P.; Dallas, A.; Reardon, C.; Kubo, R.; Shinnick, T.","year":"1990","unstructured":"Born W, Happ MP, Dallas A, Reardon C, Kubo R, Shinnick T, et al. Recognition of heat-shock-proteins and yo T cell function. Immunol Today 1990; 11: 40-3.","journal-title":"Immunol Today"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.1136\/gut.32.11.1412","article-title":"Increase in y\/ T cell receptor bearing lymphocytes in normal small bowel mucosa in latent coeliac disease","volume":"32","author":"Maki, M.; Holm, K.; Collin, P.; Salivahti, E.","year":"1991","unstructured":"Maki M, Holm K, Collin P, Salivahti E. Increase in y\/ T cell receptor bearing lymphocytes in normal small bowel mucosa in latent coeliac disease. Gut 1991; 32: 1412-4.","journal-title":"Gut"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1084\/jem.175.3.695","article-title":"Immunoregulatory functions for murine intraepithelial lymphocytes: yoh T cell receptorpositive (TCR+) T cells abrogate oral tolerance, while (t\/B TCR+ T cells provide B cell help","volume":"175","author":"Fujihashi, K.; Taguchi, T.; Aicher, W.K.; McGhee, JR, Bluestone; JA, Eldridge; J.H.","year":"1992","unstructured":"Fujihashi K, Taguchi T, Aicher WK, McGhee JR, Bluestone JA, Eldridge JH, et al. Immunoregulatory functions for murine intraepithelial lymphocytes: yoh T cell receptorpositive (TCR+) T cells abrogate oral tolerance, while (t\/B TCR+ T cells provide B cell help. ] Exp Med 1992, 175: 695-707.","journal-title":"Exp Med"}],"container-title":["Gut"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/gut.34.2.208","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T03:26:26Z","timestamp":1765596386000},"score":1,"resource":{"primary":{"URL":"https:\/\/gut.bmj.com\/lookup\/doi\/10.1136\/gut.34.2.208"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1993,2]]},"references-count":22,"journal-issue":{"issue":"2","published-online":{"date-parts":[[1993,2,1]]},"published-print":{"date-parts":[[1993,2]]}},"alternative-id":["10.1136\/gut.34.2.208"],"URL":"https:\/\/doi.org\/10.1136\/gut.34.2.208","relation":{},"ISSN":["0017-5749","1468-3288"],"issn-type":[{"value":"0017-5749","type":"print"},{"value":"1468-3288","type":"electronic"}],"subject":[],"published":{"date-parts":[[1993,2]]}}}