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PMID: 12376619 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Protection of the intestinal mucosa by intraepithelial gamma delta T cells.

Chen Y, Chou K, Fuchs E, Havran WL, Boismenu R

Abstract

gammadelta intraepithelial T lymphocytes (IEL) represent a major T cell population within the intestine of unclear functional relevance. The role of intestinal gammadelta IEL was evaluated in the dextran sodium sulfate (DSS) induced mouse colitis model system. Large numbers of gammadelta T cells, but not alphabeta T cells, were localized at sites of DSS-induced epithelial cell damage. gammadelta IEL in DSS treated mice expressed keratinocyte growth factor (KGF), a potent intestinal epithelial cell mitogen. gammadelta cell-deficient mice (TCRdelta(-/-)) and KGF-deficient mice (KGF(-/-)), but not alphabeta cell-deficient mice (TCRalpha(-/-)), were more prone than wild-type mice to DSS-induced mucosal injury and demonstrated delayed tissue repair after termination of DSS treatment. Termination of DSS treatment resulted in vigorous epithelial cell proliferation in wild-type mice but not in TCRdelta(-/-) mice or KGF(-/-) mice. These results suggest that gammadelta IEL help preserve the integrity of damaged epithelial surfaces by providing the localized delivery of an epithelial cell growth factor.

MeSH Terms
Animals Cell Division Colitis/chemically induced,immunology,pathology Dextran Sulfate/adverse effects Disease Models, Animal Epithelial Cells/cytology Fibroblast Growth Factor 7 Fibroblast Growth Factors/genetics,immunology Genetic Predisposition to Disease/genetics Intestinal Mucosa/cytology,immunology Mice Mice, Inbred C57BL Mice, Knockout Receptors, Antigen, T-Cell, gamma-delta/genetics,immunology T-Lymphocytes/immunology Time Factors
Chemicals
Fgf7 protein, mouse Receptors, Antigen, T-Cell, gamma-delta Fibroblast Growth Factor 7 Fibroblast Growth Factors Dextran Sulfate
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Chen Yaping
Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Chou Kevin
Fuchs Elaine
Havran Wendy L
Boismenu Richard
References (47)
47 references, click to expand
  1. Clinicopathologic study of dextran sulfate sodium experimental murine colitis.
    Lab Invest. 1993 Aug;69(2):238-49 PMID: 8350599
  2. T cell receptor delta gene mutant mice: independent generation of alpha beta T cells and programmed rearrangements of gamma delta TCR genes.
    Cell. 1993 Feb 12;72(3):337-48 PMID: 8381716
  3. Keratinocyte growth factor is a growth factor for type II pneumocytes in vivo.
    J Clin Invest. 1994 Mar;93(3):1298-306 PMID: 8132770
  4. Keratinocyte growth factor is a growth factor for mammary epithelium in vivo. The mammary epithelium of lactating rats is resistant to the proliferative action of keratinocyte growth factor.
    Am J Pathol. 1994 May;144(5):862-8 PMID: 8178937
  5. Increase of circulating gamma/delta T lymphocytes in the peripheral blood of patients affected by active inflammatory bowel disease.
    Clin Exp Immunol. 1994 Oct;98(1):83-8 PMID: 7923890
  6. Dextran sulfate sodium-induced colitis occurs in severe combined immunodeficient mice.
    Gastroenterology. 1994 Dec;107(6):1643-52 PMID: 7958674
  7. Keratinocyte growth factor induces proliferation of hepatocytes and epithelial cells throughout the rat gastrointestinal tract.
    J Clin Invest. 1994 Nov;94(5):1764-77 PMID: 7962522
  8. The function of KGF in morphogenesis of epithelium and reepithelialization of wounds.
    Science. 1994 Nov 4;266(5186):819-22 PMID: 7973639
  9. Modulation of epithelial cell growth by intraepithelial gamma delta T cells.
    Science. 1994 Nov 18;266(5188):1253-5 PMID: 7973709
  10. Homeostatic regulation of intestinal epithelia by intraepithelial gamma delta T cells.
    Proc Natl Acad Sci U S A. 1995 Jun 20;92(13):6147-51 PMID: 7597094
  11. Experimental models of inflammatory bowel disease.
    Gastroenterology. 1995 Oct;109(4):1344-67 PMID: 7557106
  12. Self-reactive cytotoxic gamma delta T lymphocytes in Graves' disease specifically recognize thyroid epithelial cells.
    J Immunol. 1996 Jan 15;156(2):804-11 PMID: 8543836
  13. Keratinocyte growth factor is required for hair development but not for wound healing.
    Genes Dev. 1996 Jan 15;10(2):165-75 PMID: 8566750
  14. Increased expression of keratinocyte growth factor messenger RNA associated with inflammatory bowel disease.
    Gastroenterology. 1996 Feb;110(2):441-51 PMID: 8566591
  15. Keratinocyte growth factor ameliorates mucosal injury in an experimental model of colitis in rats.
    Gastroenterology. 1996 Apr;110(4):1077-83 PMID: 8612996
  16. Human intestinal Vdelta1+ lymphocytes recognize tumor cells of epithelial origin.
    J Exp Med. 1996 Apr 1;183(4):1681-96 PMID: 8666926
  17. Dextran sulfate sodium (DSS) induced experimental colitis in immunodeficient mice: effects in CD4(+) -cell depleted, athymic and NK-cell depleted SCID mice.
    Inflamm Res. 1996 Apr;45(4):181-91 PMID: 8741008
  18. Cytokine imbalance and autoantibody production in T cell receptor-alpha mutant mice with inflammatory bowel disease.
    J Exp Med. 1996 Mar 1;183(3):847-56 PMID: 8642289
  19. Increased frequency of abnormal gamma delta T cells in blood of patients with inflammatory bowel diseases.
    J Immunol. 1996 Mar 15;156(6):2331-9 PMID: 8690925
  20. Keratinocyte growth factor is highly overexpressed in inflammatory bowel disease.
    Am J Pathol. 1996 Aug;149(2):521-9 PMID: 8701991
  21. Keratinocyte growth factor ameliorates radiation- and bleomycin-induced lung injury and mortality.
    Am J Pathol. 1996 Dec;149(6):1963-70 PMID: 8952531
  22. Changes in human mucosal gamma delta T cell repertoire and function associated with the disease process in inflammatory bowel disease.
    Mol Med. 1997 Mar;3(3):183-203 PMID: 9100225
  23. CD4+ T-cell population mediates development of inflammatory bowel disease in T-cell receptor alpha chain-deficient mice.
    Gastroenterology. 1997 Jun;112(6):1876-86 PMID: 9178680
  24. Cloning of mouse FGF10 and up-regulation of its gene expression during wound healing.
    Gene. 1997 Sep 15;197(1-2):399-404 PMID: 9332392
  25. Mouse fibroblast growth factor 10: cDNA cloning, protein characterization, and regulation of mRNA expression.
    Oncogene. 1997 Oct;15(18):2211-8 PMID: 9393979
  26. Recognition of stress-induced MHC molecules by intestinal epithelial gammadelta T cells.
    Science. 1998 Mar 13;279(5357):1737-40 PMID: 9497295
  27. Current concepts in mucosal immunity. III. Ontogeny and function of gamma delta T cells in the intestine.
    Am J Physiol. 1998 Mar;274(3 Pt 1):G455-8 PMID: 9530144
  28. Characterization of recombinant human fibroblast growth factor (FGF)-10 reveals functional similarities with keratinocyte growth factor (FGF-7).
    J Biol Chem. 1998 May 22;273(21):13230-5 PMID: 9582367
  29. The critical role of interleukin 4 but not interferon gamma in the pathogenesis of colitis in T-cell receptor alpha mutant mice.
    Gastroenterology. 1999 Feb;116(2):320-6 PMID: 9922312
  30. Clonal expansion of CD4+ TCRbetabeta+ T cells in TCR alpha-chain- deficient mice by gut-derived antigens.
    J Immunol. 1999 Feb 1;162(3):1843-50 PMID: 9973450
  31. Biological insights into TCRgammadelta+ and TCRalphabeta+ intraepithelial lymphocytes provided by serial analysis of gene expression (SAGE).
    Immunity. 2001 Sep;15(3):419-34 PMID: 11567632
  32. Intraepithelial lymphocytes: exploring the Third Way in immunology.
    Nat Immunol. 2001 Nov;2(11):997-1003 PMID: 11685222
  33. rHuKGF ameliorates symptoms in DSS and CD4(+)CD45RB(Hi) T cell transfer mouse models of inflammatory bowel disease.
    Am J Physiol Gastrointest Liver Physiol. 2002 Apr;282(4):G690-701 PMID: 11897629
  34. A role for skin gammadelta T cells in wound repair.
    Science. 2002 Apr 26;296(5568):747-9 PMID: 11976459
  35. Gammadelta T cells: functional plasticity and heterogeneity.
    Nat Rev Immunol. 2002 May;2(5):336-45 PMID: 12033739
  36. Human KGF is FGF-related with properties of a paracrine effector of epithelial cell growth.
    Science. 1989 Aug 18;245(4919):752-5 PMID: 2475908
  37. A novel method in the induction of reliable experimental acute and chronic ulcerative colitis in mice.
    Gastroenterology. 1990 Mar;98(3):694-702 PMID: 1688816
  38. Attributes of gammadelta intraepithelial lymphocytes as suggested by their transcriptional profile.
    Proc Natl Acad Sci U S A. 2001 Aug 28;98(18):10261-6 PMID: 11526237
  39. Human keratinocyte growth factor effects in a porcine model of epidermal wound healing.
    J Exp Med. 1993 Sep 1;178(3):865-78 PMID: 8350059
  40. Expression cDNA cloning of the KGF receptor by creation of a transforming autocrine loop.
    Science. 1991 Jan 4;251(4989):72-5 PMID: 1846048
  41. 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. 1991 Jun;84(3):440-4 PMID: 1828397
  42. Recognition of self antigens by skin-derived T cells with invariant gamma delta antigen receptors.
    Science. 1991 Jun 7;252(5011):1430-2 PMID: 1828619
  43. Immunohistochemical characterization, distribution, and ultrastructure of lymphocytes bearing T-cell receptor gamma/delta in inflammatory bowel disease.
    Gastroenterology. 1991 Sep;101(3):670-8 PMID: 1860632
  44. Determination of ligand-binding specificity by alternative splicing: two distinct growth factor receptors encoded by a single gene.
    Proc Natl Acad Sci U S A. 1992 Jan 1;89(1):246-50 PMID: 1309608
  45. A confined variable region confers ligand specificity on fibroblast growth factor receptors: implications for the origin of the immunoglobulin fold.
    EMBO J. 1992 May;11(5):1885-90 PMID: 1316275
  46. Large induction of keratinocyte growth factor expression in the dermis during wound healing.
    Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):6896-900 PMID: 1379725
  47. Stimulation of all epithelial elements during skin regeneration by keratinocyte growth factor.
    J Exp Med. 1994 Mar 1;179(3):831-40 PMID: 7509362
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
2002-10-29
Epub
2002-00-10
Pages
14338-43
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC137885
Subset
IM
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