Advertisement

Intraepitheliale Lymphozyten: Die erste Garde einer Immunabwehr?

  • W. Holtmeier
Conference paper

Zusammenfassung

Die Funktionen intraepithelialer Lymphozyten (IEL) sind weitgehend unge-klärt. Aufgrund ihrer Lokalisation in der Darmmukosa wird postuliert, daß IEL die erste Garde einer Immunabwehr bilden. Da sie die ersten Immunzellen sind, die mit potentiell gefährlichen Antigenen, wie z.B. invasiven Mikroorganismen in Kontakt treten, ist davon auszugehen, daß diese Zellpopulation entscheidend an der Initiierung einer Immunabwehr beteiligt ist. Bislang ist jedoch nur sehr wenig darüber bekannt, wie IEL ihre vermeintliche Rolle als Wächter des Epithels wahrnehmen könnten. IEL sind von der Lamina propria nur durch die Basalmembran getrennt. Es wäre daher vorstellbar, daß IEL durch die Sekretion von Botenstoffen (Zytokinen) Kontakt mit den Immunzellen der Lamina propria aufnehmen und diese zur Immunabwehr rekrutieren (s. Abb. 1). Weiterhin würde es der direkte Kontakt zu den Epithelzellen erlauben, daß transformierte bzw. infizierte Epithelzellen eliminiert werden und IEL somit auch an der Aufrechterhaltung und Integrität der Epithelschicht beteiligt sind.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Literatur

  1. 1.
    Balk SP, Ebert EC, Blumenthal RL, McDermott FV, Wucherpfennig KW, Landau SB, Blumberg RS (1991) Oligoclonal expansion and CD1 recognition by human intestinal intraepithelial lymphocytes. Science 253: 1411–1415PubMedCrossRefGoogle Scholar
  2. 2.
    Beagley KW, Fujihashi K, Black CA, Lagoo AS, Yamamoto M, McGhee JR, Kiyono H (1993) The Mycobacterium tuberculosis 71-kDa heat-shock protein induces proliferation and cytokine secretion by murine gut intraepithelial lymphocytes. Eur J Immunol 23: 2049–2052PubMedCrossRefGoogle Scholar
  3. 3.
    Beckman EM, Porcelli SA, Morita CT, Behar SM, Furlong ST, Brenner MB (1994) Recognition of a lipid antigen by CD 1-restricted α/ß T cells [see comments]. Nature 372: 691–694PubMedCrossRefGoogle Scholar
  4. 4.
    Beldjord K, Beldjord C, Macintyre E, Even P, Sigaux F (1993) Peripheral selection of V81+ cells with restricted T cell receptor 8 gene junctional repertoire in the peripheral blood of healthy donors. J Exp Med 178: 121–127PubMedCrossRefGoogle Scholar
  5. 5.
    Blumberg RS, Balk SP (1994) Intraepithelial lymphocytes and their recognition of non-classical MHC molecules. Int Rev Immunol 11: 15–30PubMedCrossRefGoogle Scholar
  6. 6.
    Blumberg RS, Yockey CE, Gross GG, Ebert EC, Balk SP (1993) Human intestinal intraepithelial lymphocytes are derived from a limited number of T cell clones that utilize multiple Vß T cell receptor genes. J Immunol 150: 5144–5153PubMedGoogle Scholar
  7. 7.
    Boismenu R, Havran WL (1994) Modulation of epithelial cell growth by intraepithelial γ/δ T cells. Science 266: 1253–1255PubMedCrossRefGoogle Scholar
  8. 8.
    Bonneville M, Janeway CA, Ito K, Haser W, Ishida I, Nakanishi N, Tonegawa S (1988) Intestinal intraepithelial lymphocytes are a distinct set of γ/δ T cells. Nature 336: 479–481PubMedCrossRefGoogle Scholar
  9. 9.
    Born W, Hall L, Dallas A, Boymel J, Shinnick T, Young D, Brennan P, O’Brien R (1990) Recognition of a peptide antigen by heat shock—reactive γ/δ T lymphocytes. Science 249: 67 - 69PubMedCrossRefGoogle Scholar
  10. 10.
    Borst J, Wicherink A, van Dongen J J, de Vries E, Comans-Bitter WM, Wassenaar F, Van den Elsen P (1989) Non-random expression of T cell receptor γ and δ variable gene segments in functional T lymphocyte clones from human peripheral blood. Eur J Immunol 19: 1559–1568Google Scholar
  11. 11.
    Breit TM, Wolvers-Tettero IL, van Dongen JJ (1994) Unique selection determinant in polyclonal Vδ2-Jδ junctional regions of human peripheral γ/δ T lymphocytes. J Immunol 152: 2860–2864PubMedGoogle Scholar
  12. 12.
    Cerf-Bensussan N, Guy-Grand D (1991) Intestinal intraepithelial lymphocytes. Gastroenterol Clin North Am 20: 549–576PubMedGoogle Scholar
  13. 13.
    Chien YH, Iwashima M, Kaplan KB, Elliott JF, Davis MM (1987) A new T-cell receptor gene located within the a locus and expressed early in T-cell differentiation. Nature 327: 677–682PubMedCrossRefGoogle Scholar
  14. 14.
    Choi Y, Lafferty JA, Clements JR, Todd JK, Gelfand EW, Kappler J, Marrack P, Kotzin BL (1990) Selective expansion of T cells expressing Vß2 in toxic shock syndrome. J Exp Med 172: 981–984PubMedCrossRefGoogle Scholar
  15. 15.
    Chowers Y, Holtmeier W, Harwood J, Morzycka-Wroblewska E, Kagnoff MF (1994) The Vδ1 T cell receptor repertoire in human small intestine and colon. J Exp Med 180: 183–190PubMedCrossRefGoogle Scholar
  16. 16.
    Chowers Y, Holtmeier W, Morzycka-Wroblewska E, Kagnoff MF (1995) Inverse PCR amplification of rare T cell receptor δ messages from mucosal biopsy specimens. J Immunol Methods 179: 261–263PubMedCrossRefGoogle Scholar
  17. 17.
    Cole DJ, Weil DP, Shamamian P, Rivoltini L, Kawakami Y, Topalian S, Jennings C, Eliyahu S, Rosenberg SA, Nishimura MI (1994) Identification of MART-1-specific T-cell receptors:Google Scholar
  18. 18.
    T cells utilizing distinct T-cell receptor variable and joining regions recognize the same tumor epitope. Cancer Res 54:5265–5268Google Scholar
  19. 19.
    Davis MM, Bjorkman PJ (1988) T-cell antigen receptor genes and T-cell recognition [published erratum appears in Nature 1988 Oct 20;335(6192):744]. Nature 334: 395–402PubMedCrossRefGoogle Scholar
  20. 20.
    Davodeau F, Peyrat MA, Hallet MM, Houde I, Vie H, Bonneville M (1993) Peripheral selection of antigen receptor junctional features in a major human γ/δ subset. Eur J Immunol 23: 804–808PubMedCrossRefGoogle Scholar
  21. 21.
    Deusch K, Luling F, Reich K, Classen M, Wagner H, Pfeffer K (1991) A major fraction of human intraepithelial lymphocytes simultaneously expresses the γ/δ T cell receptor, the CD8 accessory molecule and preferentially uses the Vδ1 gene segment. Eur J Immunol 21: 1053–1059PubMedCrossRefGoogle Scholar
  22. 22.
    Fitzgerald JE, Ricalton NS, Meyer AC, West SG, Kaplan H, Behrendt C, Kotzin BL (1995) Analysis of clonal CD8+ T cell expansions in normal individuals and patients with rheumatoid arthritis. J Immunol 154: 3538–3547PubMedGoogle Scholar
  23. 23.
    Geneveé C, Chung V, Diu A, Hercend T, Triebel F (1994) TCR gene segments from at least one third of Vα subfamilies rearrange at the δ locus. Mol Immunol 31: 109–115PubMedCrossRefGoogle Scholar
  24. 24.
    Giachino C, Granziero L, Modena V, Maiocco V, Lomater C, Fantini F, Lanzavecchia A, Migone N (1994) Clonal expansions of Vδ1+ and Vδ2+ cells increase with age and limit the repertoire of human γ/δ T cells. Eur J Immunol 24: 1914–1918PubMedCrossRefGoogle Scholar
  25. 25.
    Groh V, Porcelli S, Fabbi M, Lanier LL, Picker LJ, Anderson T, Warnke RA, Bhan AK, Strominger JL, Brenner MB (1989) Human lymphocytes bearing T cell receptor γ/δ are phenotypically diverse and evenly distributed throughout the lymphoid system. J Exp Med 169: 1277–1294PubMedCrossRefGoogle Scholar
  26. 26.
    Gross GG, Schwartz VL, Stevens C, Ebert EC, Blumberg RS, Balk SP (1994) Distribution of dominant T cell receptor ß chains in human intestinal mucosa. J Exp Med 180: 1337–1344PubMedCrossRefGoogle Scholar
  27. 27.
    Guglielmi P, Davi F, D’Auriol L, Bories J-C, Dausset J, Bensussan A (1988) Use of a variable a region to create a functional T-cell receptor δ chain. Proc Natl Acad Sci USA 85: 5634–5638PubMedCrossRefGoogle Scholar
  28. 28.
    Haas W, Pereira P, Tonegawa S (1993) γ/δ cells. Annu Rev Immunol 11: 637–685Google Scholar
  29. 29.
    Havran WL, Chien YH, Allison JP (1991) Recognition of self antigens by skin-derived T cells with invariant γ/δ antigen receptors. Science 252: 1430–1432PubMedCrossRefGoogle Scholar
  30. 30.
    Hedrick SM, Engel I, McElligott DL, Fink PJ, Hsu ML, Hansburg D, Matis LA (1988) Selection of amino acid sequences in the ß chain of the T cell antigen receptor. Science 239: 1541–1544PubMedCrossRefGoogle Scholar
  31. 31.
    Heeger PS, Smoyer WE, Saad T, Albert S, Kelly CJ, Neilson EG (1994) Molecular analysis of the helper T cell response in murine interstitial nephritis. T cells recognizing an immunodominant epitope use multiple T cell receptor Vß genes with similarities across CDR3. J Clin Invest 94: 2084–2092PubMedCrossRefGoogle Scholar
  32. 32.
    Hingorani R, Choi IH, Akolkar P, Gulwani-Akolkar B, Pergolizzi R, Silver J, Gregersen PK (1993) Clonal predominance of T cell receptors within the CD8+ CD45RO+ subset in normal human subjects. J Immunol 151: 5762–5769PubMedGoogle Scholar
  33. 33.
    Holtmeier W, Chowers Y, Lumeng A, Morzycka-Wroblewska E, Kagnoff MF (1995) The δ T cell receptor repertoire in human colon and peripheral blood is oligoclonal irrespective of V region usage. J Clin Invest 96: 1108–1117PubMedCrossRefGoogle Scholar
  34. 34.
    Janeway CA (1992) The immune system evolved to discriminate infectious nonself from noninfectious self. Immunol Today 13: 11–16PubMedCrossRefGoogle Scholar
  35. 35.
    Janeway CA, Jones B, Hayday A (1988) Specificity and function of T cells bearing γ/δ receptors. Immunol Today 9: 73–76PubMedCrossRefGoogle Scholar
  36. 36.
    Jarry A, Cerf-Bensussan N, Brousse N, Selz F, Guy-Grand D (1990) Subsets of CD3+ (T cell receptor α/ß or γ/δ) and CD3- lymphocytes isolated from normal human gut epithelium display phenotypical features different from their counterparts in peripheral blood. Eur J Immunol 20: 1097–1103PubMedCrossRefGoogle Scholar
  37. 37.
    Jones CM, Lake RA, Lamb JR, Faith A (1994) Degeneracy of T cell receptor recognition of an influenza virus hemagglutinin epitope restricted by HLA-DQ and -DR class II molecules. Eur J Immunol 24: 1137–1142PubMedCrossRefGoogle Scholar
  38. 38.
    Kaufmann SHE (1993) Immunity to intracellular bacteria. Annu Rev Immunol 11: 129–163PubMedCrossRefGoogle Scholar
  39. 39.
    Kaufmann SHE (1996) γ/δ and other unconventional T Lymphocytes - What do they see and what do they do. Proc Natl Acad Sci USA 93:2272–2279Google Scholar
  40. 40.
    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 γ/δ T cells. Proc Natl Acad Sci USA 92: 6147–6151PubMedCrossRefGoogle Scholar
  41. 41.
    Loh EY, Elliott JF, Cwirla S, Lanier LL, Davis MM (1989) Polymerase chain reaction with single-sided specificity: analysis of T cell receptor 5 chain. Science 243: 217–220PubMedCrossRefGoogle Scholar
  42. 42.
    Mombaerts P, Arnoldi J, Russ F, Tonegawa S, Kaufmann SH (1993) Different roles of α/ß and γ/δ T cells in immunity against an intracellular bacterial pathogen. Nature 365: 53–56PubMedCrossRefGoogle Scholar
  43. 43.
    Moss PA, Bell JI (1995) Sequence analysis of the human α/ß T-cell receptor CDR3 region. Immunogenetics 42: 10–18PubMedCrossRefGoogle Scholar
  44. 44.
    Moss PA, Rosenberg WM, Bell JI (1992) The human T cell receptor in health and disease. Annu Rev Immunol 10: 71–96PubMedCrossRefGoogle Scholar
  45. 45.
    Pereira P, Gerber D, Huang SY, Tonegawa S (1995) Ontogenic development and tissue distribution of Vyl-expressing γ/δ T lymphocytes in normal mice. J Exp Med 182: 1921–1930PubMedCrossRefGoogle Scholar
  46. 46.
    Peyrat MA, Davodeau F, Houde I, Romagne F, Necker A, Leget C, Cervoni JP, Cerf-Bensussan N, Vie H, Bonneville M (1995) Repertoire analysis of human peripheral blood lymphocytes using a human Vδ3 region-specific monoclonal antibody. Characterization of dual T cell receptor (TCR) δ-chain expressors and α/ß T cells expressing Vδ3JαCα-encoded TCR chains. J Immunol 155: 3060–3067PubMedGoogle Scholar
  47. 47.
    Pfeffer K, Schoel B, Plesnila N, Lipford GB, Kromer S, Deusch K, Wagner H (1992) A lectin-binding, protease-resistant mycobacterial ligand specifically activates V-γ-9+ human γ/δ T cells. J Immunol 148: 575–583PubMedGoogle Scholar
  48. 48.
    Pluschke G, Taube H, Krawinkel U, Pfeffer K, Wagner H, Classen M, Deusch K (1994) Oligoclonality and skewed T cell receptor Vß gene segment expression in in vivo activated human intestinal intraepithelial T lymphocytes. Immunobiology 192: 77–93PubMedCrossRefGoogle Scholar
  49. 49.
    Porcelli S, Yockey CE, Brenner MB, Balk SP (1993) Analysis of T cell antigen receptor (TCR) expression by human peripheral blood CD4-8-α/ß T cells demonstrates preferential use of several Vß genes and an invariant TCR a chain. J Exp Med 178: 1–16PubMedCrossRefGoogle Scholar
  50. 50.
    Posnett DN, Sinha R, Kabak S, Russo C (1994) Clonal populations of T cells in normal elderly humans: the T cell equivalent to “benign monoclonal gammapathy” [published erratum appears in J Exp Med 1994 Mar 1;179(3): 1077]. J Exp Med 179: 609–618Google Scholar
  51. 51.
    Regnault A, Cumano A, Vassalli P, Guy-Grand D, Kourilsky P (1994) Oligoclonal repertoire of the CD8 α/α and the CD8 α/ß TCR-α/ß murine intestinal intraepithelial T lymphocytes: evidence for the random emergence of T cells. J Exp Med 180: 1345–1358PubMedCrossRefGoogle Scholar
  52. 52.
    Rellahan BL, Bluestone JA, Houlden BA, Cotterman MM, Matis LA (1991) Junctional sequences influence the specificity of γ/δ T cell receptors. J Exp Med 173: 503–506PubMedCrossRefGoogle Scholar
  53. 53.
    Rock EP, Sibbald PR, Davis MM, Chien YH (1994) CDR3 length in antigen-specific immune receptors. J Exp Med 179: 323–328PubMedCrossRefGoogle Scholar
  54. 54.
    Rosenberg WM, Moss PA, Bell JI (1992) Variation in human T cell receptor Vß and JP repertoire: analysis using anchor polymerase chain reaction. Eur J Immunol 22: 541–549PubMedCrossRefGoogle Scholar
  55. 55.
    Sartor RB (1996) Cytokines in Intestinal Inflammation: Pathophysiological and Clinical Considerations. Gastroenterology 106: 533–539Google Scholar
  56. 56.
    Scherer MT, Ignatowicz L, Winslow GM, Kappler JW, Marrack P (1993) Superantigens: bacterial and viral proteins that manipulate the immune system. Annu Rev Cell Biol 9: 101–128PubMedCrossRefGoogle Scholar
  57. 57.
    Schild H, Mavaddat N, Litzenberger C, Ehrich EW, Davis MM, Bluestone JA, Matis L, Draper RK, Chien YH (1994) The nature of major histocompatibility complex recognition by γ/δ T cells. Cell 76: 29–37PubMedCrossRefGoogle Scholar
  58. 58.
    Sciammas R, Johnson RM, Sperling AI, Brady W, Linsley PS, Spear PG, Fitch FW, Bluestone JA (1994) Unique antigen recognition by a herpesvirus-specific TCR-γ/δ cell. J Immunol 152: 5392–5397PubMedGoogle Scholar
  59. 59.
    Sieling PA, Chatterjee D, Porcelli SA, Prigozy TI, Mazzaccaro RJ, Soriano T, Bloom BR, Brenner MB, Kronenberg M, Brennan PJ (1995) CD 1-restricted T cell recognition of microbial lipoglycan antigens [see comments]. Science 269: 227–230PubMedCrossRefGoogle Scholar
  60. 60.
    Spencer J, Isaacson PG, Diss TC, MacDonald TT (1989) Expression of disulfide-linked and non-disulfide-linked forms of the T cell receptor γ/δ heterodimer in human intestinal intraepithelial lymphocytes. Eur J Immunol 19: 1335–1338PubMedCrossRefGoogle Scholar
  61. 61.
    Uematsu Y (1991) A novel and rapid cloning method for the T-cell receptor variable region sequences. Immunogenetics 34: 174–178PubMedCrossRefGoogle Scholar
  62. 62.
    Ullrich R, Schieferdecker HL, Ziegler K, Riecken EO, Zeitz M (1990) γ/δ T cells in the human intestine express surface markers of activation and are preferentially located in the epithelium. Cell Immunol 128: 619–627Google Scholar
  63. 63.
    Van Kerckhove C, Russell GJ, Deusch K, Reich K, Bhan AK, DerSimonian H, Brenner MB (1992) Oligoclonality of human intestinal intraepithelial T cells. J Exp Med 175: 57–63PubMedCrossRefGoogle Scholar
  64. 64.
    Viney J, MacDonald TT, Spencer J (1990) γ/δ T cells in the gut epithelium. Gut 31: 841–844Google Scholar
  65. 65.
    Weintraub BC, Jackson MR, Hedrick SM (1994) y/ô T cells can recognize nonclassical MHC in the absence of conventional antigenic peptides. J Immunol 153: 3051–3058Google Scholar
  66. 66.
    Young RA, Elliott TJ (1989) Stress proteins, infection, and immune surveillance. Cell 59: 5–8PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1996

Authors and Affiliations

  • W. Holtmeier

There are no affiliations available

Personalised recommendations