Skip to main content
Hauptrubriken
CME Facharzt-Training Webinare Zeitschriften Bücher e.Medpedia Podcast
Service
Jobbörse Info & Hilfe
Fachgebiete
Anästhesiologie Allgemeinmedizin Arbeitsmedizin Augenheilkunde Chirurgie Dermatologie Gynäkologie und Geburtshilfe HNO Innere Medizin Kardiologie Neurologie Onkologie und Hämatologie Orthopädie und Unfallchirurgie Pädiatrie Pathologie Psychiatrie Radiologie Rechtsmedizin Urologie Zahnmedizin
Themen
Klimawandel und Gesundheit Neues aus dem Markt COVID-19 Praxis und Beruf Seltene Erkrankungen GOÄ & EBM Panorama
Sammlungen
Kasuistiken Algorithmen & Infografiken Blickdiagnosen Arthropedia FlapFinder (für Dermatochirurgen) Videos Kongressberichterstattung Medizin für Apothekerinnen und Apotheker Für Ärztinnen und Ärzte in Weiterbildung Für Medizinstudierende
Erweiterte Suche
Anmelden
nach oben
International Journal of Colorectal Disease
Erschienen in: International Journal of Colorectal Disease 9/2010

01.09.2010 | Original Article

The protective effect of oral colitis-derived proteins in a murine model of inflammatory bowel disease is associated with an increase in γδ T cells in large intestinal mucosa

verfasst von: Yuefang Ye, Xi Jin, Min Yue, Shaohua Chen, Chaohui Yu, Youming Li

Erschienen in: International Journal of Colorectal Disease | Ausgabe 9/2010

Einloggen, um Zugang zu erhalten

Abstract

Backgrounds and aims

Oral tolerance has previously been shown effective in preventing several immune-mediated disorders in animal models. The aims of this study were to investigate the effect of oral colitis-extracted proteins (CEP) on dextran sulfate sodium (DSS)-induced colitis in BALB/c mice and to explore the relative role of the intestinal mucosal γδ T cells.

Methods

The effect of five low oral doses of CEP on colitis was evaluated by clinical manifestation and histological lesions. Serum cytokines were measured by enzyme-linked immunosorbent assay. The percentages of the intestinal mucosal γδ T cells were evaluated by flow cytometry.

Results

CEP-fed colitis mice showed less severe symptoms and histological injury than bovine serum albumin (BSA)-fed control mice. Tolerized mice developed an increase in TGF-β1 and no change in IFN-γ serum levels. Increases in TCRγδ+ T cells and CD8α+TCRγδ+ T cells in small intestinal mucosal lymphocytes and no quantitative change in large intestinal mucosal lymphocytes were demonstrated in colitis mice compared to untreated mice. The proportions of TCRγδ+ T cells and CD8α+TCRγδ+ T cells in large intestinal mucosal lymphocytes from CEP-fed colitis mice were significantly higher compared to BSA-fed controls. The disease activity index negatively correlated with the percentages of large intestinal mucosal γδ T cells. Furthermore, mucosal repair in repair-period mice was also accompanied by increases in TCRγδ+ T cells and CD8α+TCRγδ+ T cells in large intestinal mucosal lymphocytes.

Conclusion

Improvement of DSS-induced colitis that resulted from oral administration of colitis-extracted proteins is associated with an increase in γδ T cells in large intestinal mucosa.
Literatur
1.
2.
Hyun JG, Barrett TA (2006) Oral tolerance therapy in inflammatory bowel disease. Am J Gastroenterol 101:569–571CrossRefPubMed
3.
Whitacre CC, Gienapp IE, Meyer A, Cox KL, Javed N (1996) Oral tolerance in experimental autoimmune encephalomyelitis. Ann N Y Acad Sci 778:217–227CrossRefPubMed
4.
von Herrath MG, Dyrberg T, Oldstone MB (1996) Oral insulin treatment suppresses virus-induced antigen-specific destruction of beta cells and prevents autoimmune diabetes in transgenic mice. J Clin Invest 98:1324–1331CrossRef
5.
Ilan Y, Gotsman I, Pines M, Beinart R, Zeira M, Ohana M, Rabbani E, Engelhardt D, Nagler A (2000) Induction of oral tolerance in splenocyte recipients toward pretransplant antigens ameliorates chronic graft versus host disease in a murine model. Blood 95:3613–3619PubMed
6.
Trentham DE (1998) Oral tolerization as a treatment of rheumatoid arthritis. Rheum Dis Clin North Am 24:525–536CrossRefPubMed
7.
Ilan Y, Weksler-Zangen S, Ben-Horin S, Diment J, Sauter B, Rabbani E, Engelhardt D, Chowdhury NR, Chowdhury JR, Goldin E (2000) Treatment of experimental colitis by oral tolerance induction: a central role for suppressor lymphocytes. Am J Gastroenterol 95:966–973CrossRefPubMed
8.
Gotsman I, Shlomai A, Alper R, Rabbani E, Engelhardt D, Ilan Y (2001) Amelioration of immune-mediated experimental colitis: tolerance induction in the presence of preexisting immunity and surrogate antigen bystander effect. J Pharmacol Exp Ther 297:926–932PubMed
9.
Dasgupta A, Kesari KV, Ramaswamy KK, Amenta PS, Das KM (2001) Oral administration of unmodified colonic but not small intestinal antigens protects rats from hapten-induced colitis. Clin Exp Immunol 125:41–47CrossRefPubMed
10.
Israeli E, Goldin E, Shibolet O, Klein A, Hemed N, Engelhardt D, Rabbani E, Ilan Y (2005) Oral immune regulation using colitis extracted proteins for treatment of Crohn's disease: results of a phase I clinical trial. World J Gastroenterol 11:3105–3111PubMed
11.
Margalit M, Israeli E, Shibolet O, Zigmond E, Klein A, Hemed N, Donegan JJ, Rabbani E, Goldin E, Ilan Y (2006) A double-blind clinical trial for treatment of Crohn's disease by oral administration of Alequel, a mixture of autologous colon-extracted proteins: a patient-tailored approach. Am J Gastroenterol 101:561–568CrossRefPubMed
12.
Okayasu I, Hatakeyama S, Yamada M, Ohkusa T, Inagaki Y, Nakaya R (1990) A novel method in the induction of reliable experimental acute and chronic ulcerative colitis in mice. Gastroenterology 98:694–702PubMed
13.
Cooper HS, Murthy SN, Shah RS, Sedergran DJ (1993) Clinicopathologic study of dextran sulfate sodium experimental murine colitis. Lab Invest 69:238–249PubMed
14.
Dieleman LA, Palmen MJ, Akol H, Bloemena E, Pena AS, Meuwissen SG, Van Rees EP (1998) Chronic experimental colitis induced by dextran sulphate sodium (DSS) is characterized by Th1 and Th2 cytokines. Clin Exp Immunol 114:385–391CrossRefPubMed
15.
Kunisawa J, Takahashi I, Kiyono H (2007) Intraepithelial lymphocytes: their shared and divergent immunological behaviors in the small and large intestine. Immunol Rev 215:136–153CrossRefPubMed
16.
Cheroutre H (2005) IELs: enforcing law and order in the court of the intestinal epithelium. Immunol Rev 206:114–131CrossRefPubMed
17.
Komano H, Fujiura Y, Kawaguchi M, Matsumoto S, Hashimoto Y, Obana S, Mombaerts P, Tonegawa S, Yamamoto H, Itohara S (1995) Homeostatic regulation of intestinal epithelia by intraepithelial gamma delta T cells. Proc Natl Acad Sci U S A 92:6147–6151CrossRefPubMed
18.
Dalton JE, Cruickshank SM, Egan CE, Mears R, Newton DJ, Andrew EM, Lawrence B, Howell G, Else KJ, Gubbels MJ, Striepen B, Smith JE, White SJ, Carding SR (2006) Intraepithelial gammadelta + lymphocytes maintain the integrity of intestinal epithelial tight junctions in response to infection. Gastroenterology 131:818–829CrossRefPubMed
19.
Yang H, Antony PA, Wildhaber BE, Teitelbaum DH (2004) Intestinal intraepithelial lymphocyte gamma delta-T cell-derived keratinocyte growth factor modulates epithelial growth in the mouse. J Immunol 172:4151–4158PubMed
20.
Mengel J, Cardillo F, Aroeira LS, Williams O, Russo M, Vaz NM (1995) Anti-gamma delta T cell antibody blocks the induction and maintenance of oral tolerance to ovalbumin in mice. Immunol Lett 48:97–102CrossRefPubMed
21.
Fujihashi K, Dohi T, Kweon MN, McGhee JR, Koga T, Cooper MD, Tonegawa S, Kiyono H (1999) gammadelta T cells regulate mucosally induced tolerance in a dose-dependent fashion. Int Immunol 11:1907–1916CrossRefPubMed
22.
Ke Y, Pearce K, Lake JP, Ziegler HK, Kapp JA (1997) Gamma delta T lymphocytes regulate the induction and maintenance of oral tolerance. J Immunol 158:3610–3618PubMed
23.
Locke NR, Stankovic S, Funda DP, Harrison LC (2006) TCR gamma delta intraepithelial lymphocytes are required for self-tolerance. J Immunol 176:6553–6559PubMed
24.
Kapp JA, Kapp LM, McKenna KC, Lake JP (2004) gammadelta T-cell clones from intestinal intraepithelial lymphocytes inhibit development of CTL responses ex vivo. Immunology 111:155–164CrossRefPubMed
25.
Kawaguchi-Miyashita M, Shimada S, Matsuoka Y, Ohwaki M, Nanno M (2000) Activation of T-cell receptor-gammadelta + cells in the intestinal epithelia of KN6 transgenic mice. Immunology 101:38–45CrossRefPubMed
26.
Meresse B, Chen Z, Ciszewski C, Tretiakova M, Bhagat G, Krausz TN, Raulet DH, Lanier LL, Groh V, Spies T, Ebert EC, Green PH, Jabri B (2004) Coordinated induction by IL15 of a TCR-independent NKG2D signaling pathway converts CTL into lymphokine-activated killer cells in celiac disease. Immunity 21:357–366CrossRefPubMed
27.
Nanno M, Kanari Y, Naito T, Inoue N, Hisamatsu T, Chinen H, Sugimoto K, Shimomura Y, Yamagishi H, Shiohara T, Ueha S, Matsushima K, Suematsu M, Mizoguchi A, Hibi T, Bhan AK, Ishikawa H (2008) Exacerbating role of gammadelta T cells in chronic colitis of T-cell receptor alpha mutant mice. Gastroenterology 134:481–490CrossRefPubMed
28.
Nanno M, Shiohara T, Yamamoto H, Kawakami K, Ishikawa H (2007) gammadelta T cells: firefighters or fire boosters in the front lines of inflammatory responses. Immunol Rev 215:103–113CrossRefPubMed
29.
Kuhl AA, Pawlowski NN, Grollich K, Loddenkemper C, Zeitz M, Hoffmann JC (2007) Aggravation of intestinal inflammation by depletion/deficiency of gammadelta T cells in different types of IBD animal models. J Leukoc Biol 81:168–175CrossRefPubMed
30.
Chen Y, Chou K, Fuchs E, Havran WL, Boismenu R (2002) Protection of the intestinal mucosa by intraepithelial gamma delta T cells. Proc Natl Acad Sci U S A 99:14338–14343CrossRefPubMed
31.
Inagaki-Ohara K, Chinen T, Matsuzaki G, Sasaki A, Sakamoto Y, Hiromatsu K, Nakamura-Uchiyama F, Nawa Y, Yoshimura A (2004) Mucosal T cells bearing TCRgammadelta play a protective role in intestinal inflammation. J Immunol 173:1390–1398PubMed
32.
Tsuchiya T, Fukuda S, Hamada H, Nakamura A, Kohama Y, Ishikawa H, Tsujikawa K, Yamamoto H (2003) Role of gamma delta T cells in the inflammatory response of experimental colitis mice. J Immunol 171:5507–5513PubMed
33.
McVay LD, Li B, Biancaniello R, Creighton MA, Bachwich D, Lichtenstein G, Rombeau JL, Carding SR (1997) Changes in human mucosal gamma delta T cell repertoire and function associated with the disease process in inflammatory bowel disease. Mol Med 3:183–203PubMed
34.
Trejdosiewicz LK, Calabrese A, Smart CJ, Oakes DJ, Howdle PD, Crabtree JE, Losowsky MS, Lancaster F, Boylston AW (1991) Gamma delta T cell receptor-positive cells of the human gastrointestinal mucosa: occurrence and V region gene expression in Heliobacter pylori-associated gastritis, coeliac disease and inflammatory bowel disease. Clin Exp Immunol 84:440–444PubMed
35.
Fukushima K, Masuda T, Ohtani H, Sasaki I, Funayama Y, Matsuno S, Nagura H (1991) Immunohistochemical characterization, distribution, and ultrastructure of lymphocytes bearing T-cell receptor gamma/delta in inflammatory bowel disease. Gastroenterology 101:670–678PubMed
36.
Resendiz-Albor AA, Esquivel R, Lopez-Revilla R, Verdin L, Moreno-Fierros L (2005) Striking phenotypic and functional differences in lamina propria lymphocytes from the large and small intestine of mice. Life Sci 76:2783–2803CrossRefPubMed
37.
Neurath MF, Fuss I, Kelsall BL, Presky DH, Waegell W, Strober W (1996) Experimental granulomatous colitis in mice is abrogated by induction of TGF-beta-mediated oral tolerance. J Exp Med 183:2605–2616CrossRefPubMed
38.
Elson CO, Beagley KW, Sharmanov AT, Fujihashi K, Kiyono H, Tennyson GS, Cong Y, Black CA, Ridwan BW, McGhee JR (1996) Hapten-induced model of murine inflammatory bowel disease: mucosa immune responses and protection by tolerance. J Immunol 157:2174–2185PubMed
39.
Dasgupta A, Ramaswamy K, Giraldo J, Taniguchi M, Amenta PS, Das KM (2001) Colon epithelial cellular protein induces oral tolerance in the experimental model of colitis by trinitrobenzene sulfonic acid. J Lab Clin Med 138:257–269CrossRefPubMed
40.
Hoffmann JC, Pawlowski NN, Grollich K, Loddenkemper C, Zeitz M, Kuhl AA (2008) Gammadelta T lymphocytes: a new type of regulatory T cells suppressing murine 2, 4, 6-trinitrobenzene sulphonic acid (TNBS)-induced colitis. Int J Colorectal Dis 23:909–920CrossRefPubMed
41.
Ke Y, Kapp JA (1996) Oral antigen inhibits priming of CD8+ CTL, CD4+ T cells, and antibody responses while activating CD8+ suppressor T cells. J Immunol 156:916–921PubMed
42.
Pomie C, Menager-Marcq I, van Meerwijk JP (2008) Murine CD8+ regulatory T lymphocytes: the new era. Hum Immunol 69:708–714CrossRefPubMed
Metadaten
Titel
The protective effect of oral colitis-derived proteins in a murine model of inflammatory bowel disease is associated with an increase in γδ T cells in large intestinal mucosa
verfasst von
Yuefang Ye
Xi Jin
Min Yue
Shaohua Chen
Chaohui Yu
Youming Li
Publikationsdatum
01.09.2010
Verlag
Springer-Verlag
Erschienen in
International Journal of Colorectal Disease / Ausgabe 9/2010
Print ISSN: 0179-1958
Elektronische ISSN: 1432-1262
DOI
https://doi.org/10.1007/s00384-010-0975-9

Weitere Artikel der Ausgabe 9/2010

International Journal of Colorectal Disease 9/2010 Zur Ausgabe

Original Article

Electromechanical characteristics of the human colon in vitro: is there any difference between the right and left colon?

Original Article

Amelioration of dextran sulfate sodium-induced colitis by neuropeptide Y antisense oligodeoxynucleotide

Letter to the Editor

Local excision of rectal cancer afterchemoradiation: feasibility depends on the primary stage

Original Article

Measurable learning effects after a 1-week skills course in digestive surgery

Letter to the Editor

Recurrent pericarditis in a patient with ulcerative proctitis due to mesalazine suppositories

Original Article

Can DNA sampling from the rectal mucosa be a novel tool for the detection of colorectal cancer?

Neu im Fachgebiet Chirurgie

23.04.2024 | Ablationstherapie | Nachrichten

Wie erfolgreich ist eine Re-Ablation nach Rezidiv?

23.04.2024 | Appendizitis | Nachrichten

Hinter dieser Appendizitis steckte ein Erreger

23.04.2024 | Operationsvorbereitung | Nachrichten

Mehr Schaden als Nutzen durch präoperatives Aussetzen von GLP-1-Agonisten?

19.04.2024 | EAU 2024 | Kongressbericht | Nachrichten

Ureterstriktur: Innovative OP-Technik bewährt sich
weitere anzeigen

Update Chirurgie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Aktuelle BDC Leitlinien-Webinare

S3-Leitlinie „Diagnostik und Therapie des Karpaltunnelsyndroms“

Karpaltunnelsyndrom BDC Leitlinien Webinare
CME: 2 Punkte

Das Karpaltunnelsyndrom ist die häufigste Kompressionsneuropathie peripherer Nerven. Obwohl die Anamnese mit dem nächtlichen Einschlafen der Hand (Brachialgia parästhetica nocturna) sehr typisch ist, ist eine klinisch-neurologische Untersuchung und Elektroneurografie in manchen Fällen auch eine Neurosonografie erforderlich. Im Anfangsstadium sind konservative Maßnahmen (Handgelenksschiene, Ergotherapie) empfehlenswert. Bei nicht Ansprechen der konservativen Therapie oder Auftreten von neurologischen Ausfällen ist eine Dekompression des N. medianus am Karpaltunnel indiziert.

Prof. Dr. med. Gregor Antoniadis
Berufsverband der Deutschen Chirurgie e.V.

S2e-Leitlinie „Distale Radiusfraktur“

Radiusfraktur BDC Leitlinien Webinare
CME: 2 Punkte

Das Webinar beschäftigt sich mit Fragen und Antworten zu Diagnostik und Klassifikation sowie Möglichkeiten des Ausschlusses von Zusatzverletzungen. Die Referenten erläutern, welche Frakturen konservativ behandelt werden können und wie. Das Webinar beantwortet die Frage nach aktuellen operativen Therapiekonzepten: Welcher Zugang, welches Osteosynthesematerial? Auf was muss bei der Nachbehandlung der distalen Radiusfraktur geachtet werden?

PD Dr. med. Oliver Pieske
Dr. med. Benjamin Meyknecht
Berufsverband der Deutschen Chirurgie e.V.

S1-Leitlinie „Empfehlungen zur Therapie der akuten Appendizitis bei Erwachsenen“

Appendizitis BDC Leitlinien Webinare
CME: 2 Punkte

Inhalte des Webinars zur S1-Leitlinie „Empfehlungen zur Therapie der akuten Appendizitis bei Erwachsenen“ sind die Darstellung des Projektes und des Erstellungswegs zur S1-Leitlinie, die Erläuterung der klinischen Relevanz der Klassifikation EAES 2015, die wissenschaftliche Begründung der wichtigsten Empfehlungen und die Darstellung stadiengerechter Therapieoptionen.

Dr. med. Mihailo Andric
Berufsverband der Deutschen Chirurgie e.V.