Skip to main content
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1994 Oct;98(1):83–88. doi: 10.1111/j.1365-2249.1994.tb06611.x

Increase of circulating gamma/delta T lymphocytes in the peripheral blood of patients affected by active inflammatory bowel disease.

R Giacomelli 1, I Parzanese 1, G Frieri 1, A Passacantando 1, F Pizzuto 1, T Pimpo 1, P Cipriani 1, A Viscido 1, R Caprilli 1, G Tonietti 1
PMCID: PMC1534185  PMID: 7923890

Abstract

In order to study the role of gamma/delta T cells in the pathogenesis of inflammatory bowel disease (IBD) in humans, we measured the percentage of these cells in the peripheral blood, assessed the ratio of the non-disulphide-linked (delta TCS1) type of T cell receptor (TCR) in the total gamma/delta T cells, studied the co-expression of gamma/delta TCR and accessory molecules CD8 and CD16, and compared these data with both the type and the activity of the disease. Percentage levels and absolute numbers of gamma/delta+ T cells were higher in active patients than in controls (P < 0.05), mainly as a result of an increase of V delta 1+ (delta TCS1) T cell subset (P < 0.05). This trend was strongly retained independently of disease activity and clinical picture. An increased percentage of TCR delta 1+/CD16+ cells was observed in our patients compared with controls (P < 0.05). In contrast, no difference was observed as far as the TCR delta 1+/CD8+ cells were concerned. These results suggest that IBD is associated with an expansion of gamma/delta T cells in peripheral blood, which may play a role in the pathogenesis of these disorders.

Full text

PDF
83

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Asarnow D. M., Goodman T., LeFrancois L., Allison J. P. Distinct antigen receptor repertoires of two classes of murine epithelium-associated T cells. Nature. 1989 Sep 7;341(6237):60–62. doi: 10.1038/341060a0. [DOI] [PubMed] [Google Scholar]
  2. BARON J. H., CONNELL A. M., LENNARD-JONES J. E. VARIATION BETWEEN OBSERVERS IN DESCRIBING MUCOSAL APPEARANCES IN PROCTOCOLITIS. Br Med J. 1964 Jan 11;1(5375):89–92. doi: 10.1136/bmj.1.5375.89. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bertotto A., Gerli R., Spinozzi F., Muscat C., Scalise F., Castellucci G., Sposito M., Candio F., Vaccaro R. Lymphocytes bearing the gamma delta T cell receptor in acute Brucella melitensis infection. Eur J Immunol. 1993 May;23(5):1177–1180. doi: 10.1002/eji.1830230531. [DOI] [PubMed] [Google Scholar]
  4. Bonneville M., Janeway C. A., Jr, Ito K., Haser W., Ishida I., Nakanishi N., Tonegawa S. Intestinal intraepithelial lymphocytes are a distinct set of gamma delta T cells. Nature. 1988 Dec 1;336(6198):479–481. doi: 10.1038/336479a0. [DOI] [PubMed] [Google Scholar]
  5. Braakman E., van de Winkel J. G., van Krimpen B. A., Jansze M., Bolhuis R. L. CD16 on human gamma delta T lymphocytes: expression, function, and specificity for mouse IgG isotypes. Cell Immunol. 1992 Aug;143(1):97–107. doi: 10.1016/0008-8749(92)90008-d. [DOI] [PubMed] [Google Scholar]
  6. Brenner M. B., McLean J., Dialynas D. P., Strominger J. L., Smith J. A., Owen F. L., Seidman J. G., Ip S., Rosen F., Krangel M. S. Identification of a putative second T-cell receptor. Nature. 1986 Jul 10;322(6075):145–149. doi: 10.1038/322145a0. [DOI] [PubMed] [Google Scholar]
  7. Brenner M. B., McLean J., Scheft H., Riberdy J., Ang S. L., Seidman J. G., Devlin P., Krangel M. S. Two forms of the T-cell receptor gamma protein found on peripheral blood cytotoxic T lymphocytes. Nature. 1987 Feb 19;325(6106):689–694. doi: 10.1038/325689a0. [DOI] [PubMed] [Google Scholar]
  8. Brenner M. B., Strominger J. L., Krangel M. S. The gamma delta T cell receptor. Adv Immunol. 1988;43:133–192. [PubMed] [Google Scholar]
  9. Dastot H., Schmid M., Gontier C., Amiot M., Mathieu-Mahul D., Bensussan A., Boumsell L. Correlation between T cell receptor gamma delta isotypic forms and cytotoxic activity: analysis with human T cell clones and lines. Cell Immunol. 1990 Feb;125(2):315–325. doi: 10.1016/0008-8749(90)90087-8. [DOI] [PubMed] [Google Scholar]
  10. Dunon D., Cooper M. D., Imhof B. A. Migration patterns of thymus-derived gamma delta T cells during chicken development. Eur J Immunol. 1993 Oct;23(10):2545–2550. doi: 10.1002/eji.1830231025. [DOI] [PubMed] [Google Scholar]
  11. Dunon D., Cooper M. D., Imhof B. A. Thymic origin of embryonic intestinal gamma/delta T cells. J Exp Med. 1993 Feb 1;177(2):257–263. doi: 10.1084/jem.177.2.257. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Ferrini S., Zarcone D., Viale M., Cerruti G., Millo R., Moretta A., Grossi C. E. Morphologic and functional characterization of human peripheral blood T cells expressing the T cell receptor gamma/delta. Eur J Immunol. 1989 Jul;19(7):1183–1188. doi: 10.1002/eji.1830190705. [DOI] [PubMed] [Google Scholar]
  13. Fiocchi C. Immune events associated with inflammatory bowel disease. Scand J Gastroenterol Suppl. 1990;172:4–12. doi: 10.3109/00365529009091902. [DOI] [PubMed] [Google Scholar]
  14. Fukushima K., Masuda T., Ohtani H., Sasaki I., Funayama Y., Matsuno S., Nagura H. Immunohistochemical characterization, distribution, and ultrastructure of lymphocytes bearing T-cell receptor gamma/delta in inflammatory bowel disease. Gastroenterology. 1991 Sep;101(3):670–678. doi: 10.1016/0016-5085(91)90524-o. [DOI] [PubMed] [Google Scholar]
  15. Gerli R., Agea E., Bertotto A., Tognellini R., Flenghi L., Spinozzi F., Velardi A., Grignani F. Analysis of T cells bearing different isotypic forms of the gamma/delta T cell receptor in patients with systemic autoimmune diseases. J Rheumatol. 1991 Oct;18(10):1504–1510. [PubMed] [Google Scholar]
  16. Grossi C. E., Ciccone E., Migone N., Bottino C., Zarcone D., Mingari M. C., Ferrini S., Tambussi G., Viale O., Casorati G. Human T cells expressing the gamma/delta T-cell receptor (TcR-1): C gamma 1- and C gamma 2-encoded forms of the receptor correlate with distinctive morphology, cytoskeletal organization, and growth characteristics. Proc Natl Acad Sci U S A. 1989 Mar;86(5):1619–1623. doi: 10.1073/pnas.86.5.1619. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. 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 Feb 1;173(2):471–481. doi: 10.1084/jem.173.2.471. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Guy-Grand D., Malassis-Seris M., Briottet C., Vassalli P. Cytotoxic differentiation of mouse gut thymodependent and independent intraepithelial T lymphocytes is induced locally. Correlation between functional assays, presence of perforin and granzyme transcripts, and cytoplasmic granules. J Exp Med. 1991 Jun 1;173(6):1549–1552. doi: 10.1084/jem.173.6.1549. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Haas W., Kaufman S., Martinez C. The development and function of gamma delta T cells. Immunol Today. 1990 Oct;11(10):340–343. doi: 10.1016/0167-5699(90)90133-t. [DOI] [PubMed] [Google Scholar]
  20. Hara T., Mizuno Y., Takaki K., Takada H., Akeda H., Aoki T., Nagata M., Ueda K., Matsuzaki G., Yoshikai Y. Predominant activation and expansion of V gamma 9-bearing gamma delta T cells in vivo as well as in vitro in Salmonella infection. J Clin Invest. 1992 Jul;90(1):204–210. doi: 10.1172/JCI115837. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Haregewoin A., Soman G., Hom R. C., Finberg R. W. Human gamma delta+ T cells respond to mycobacterial heat-shock protein. Nature. 1989 Jul 27;340(6231):309–312. doi: 10.1038/340309a0. [DOI] [PubMed] [Google Scholar]
  22. Havlir D. V., Ellner J. J., Chervenak K. A., Boom W. H. Selective expansion of human gamma delta T cells by monocytes infected with live Mycobacterium tuberculosis. J Clin Invest. 1991 Feb;87(2):729–733. doi: 10.1172/JCI115053. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Jarry A., Cerf-Bensussan N., Brousse N., Selz F., Guy-Grand D. Subsets of CD3+ (T cell receptor alpha/beta or gamma/delta) and CD3- lymphocytes isolated from normal human gut epithelium display phenotypical features different from their counterparts in peripheral blood. Eur J Immunol. 1990 May;20(5):1097–1103. doi: 10.1002/eji.1830200523. [DOI] [PubMed] [Google Scholar]
  24. Keystone E. C., Rittershaus C., Wood N., Snow K. M., Flatow J., Purvis J. C., Poplonski L., Kung P. C. Elevation of a gamma delta T cell subset in peripheral blood and synovial fluid of patients with rheumatoid arthritis. Clin Exp Immunol. 1991 Apr;84(1):78–82. [PMC free article] [PubMed] [Google Scholar]
  25. Kluin P. M., Rust C. J., Mearin M. L., Peña A. S., Koning F. TCR gamma delta cells: antigen-driven expansion of distinct subsets based on localization and antigen specificity. Immunol Res. 1991;10(3-4):313–320. doi: 10.1007/BF02919714. [DOI] [PubMed] [Google Scholar]
  26. MacDermott R. P., Bragdon M. J., Kodner I. J., Bertovich M. J. Deficient cell-mediated cytotoxicity and hyporesponsiveness to interferon and mitogenic lectin activation by inflammatory bowel disease peripheral blood and intestinal mononuclear cells. Gastroenterology. 1986 Jan;90(1):6–11. doi: 10.1016/0016-5085(86)90067-3. [DOI] [PubMed] [Google Scholar]
  27. Markowitz J., Grancher K., Mandel F., Daum F. Immunosuppressive therapy in pediatric inflammatory bowel disease: results of a survey of the North American Society for Pediatric Gastroenterology and Nutrition. Subcommittee on Immunosuppressive Use of the Pediatric IBD Collaborative Research Forum. Am J Gastroenterol. 1993 Jan;88(1):44–48. [PubMed] [Google Scholar]
  28. Marrack P., Kappler J. The antigen-specific, major histocompatibility complex-restricted receptor on T cells. Adv Immunol. 1986;38:1–30. doi: 10.1016/s0065-2776(08)60005-x. [DOI] [PubMed] [Google Scholar]
  29. Modlin R. L., Pirmez C., Hofman F. M., Torigian V., Uyemura K., Rea T. H., Bloom B. R., Brenner M. B. Lymphocytes bearing antigen-specific gamma delta T-cell receptors accumulate in human infectious disease lesions. Nature. 1989 Jun 15;339(6225):544–548. doi: 10.1038/339544a0. [DOI] [PubMed] [Google Scholar]
  30. Morio T., Nagasawa M., Nonoyama S., Okawa H., Yata J. Phenotypic profile and functions of T cell receptor-gamma delta-bearing cells from patients with primary immunodeficiency syndrome. J Immunol. 1990 Feb 15;144(4):1270–1275. [PubMed] [Google Scholar]
  31. Okazaki K., Morita M., Nishimori I., Sano S., Toyonaga M., Nakazawa Y., Yamamoto Y., Yamamoto Y. Major histocompatibility antigen-restricted cytotoxicity in inflammatory bowel disease. Gastroenterology. 1993 Feb;104(2):384–391. doi: 10.1016/0016-5085(93)90405-2. [DOI] [PubMed] [Google Scholar]
  32. Olive C., Gatenby P. A., Serjeantson S. W. Molecular characterization of the V gamma 9 T cell receptor repertoire expressed in patients with rheumatoid arthritis. Eur J Immunol. 1992 Nov;22(11):2901–2906. doi: 10.1002/eji.1830221122. [DOI] [PubMed] [Google Scholar]
  33. Porcelli S., Brenner M. B., Band H. Biology of the human gamma delta T-cell receptor. Immunol Rev. 1991 Apr;120:137–183. doi: 10.1111/j.1600-065x.1991.tb00591.x. [DOI] [PubMed] [Google Scholar]
  34. Raulet D. H. The structure, function, and molecular genetics of the gamma/delta T cell receptor. Annu Rev Immunol. 1989;7:175–207. doi: 10.1146/annurev.iy.07.040189.001135. [DOI] [PubMed] [Google Scholar]
  35. Selmaj K., Brosnan C. F., Raine C. S. Colocalization of lymphocytes bearing gamma delta T-cell receptor and heat shock protein hsp65+ oligodendrocytes in multiple sclerosis. Proc Natl Acad Sci U S A. 1991 Aug 1;88(15):6452–6456. doi: 10.1073/pnas.88.15.6452. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Shorter R. G., McGill D. B., Bahn R. C. Cytotoxicity of mononuclear cells for autologous colonic epithelial cells in colonic diseases. Gastroenterology. 1984 Jan;86(1):13–22. [PubMed] [Google Scholar]
  37. Stenson W. F., MacDermott R. P. Immunology of inflammatory bowel disease. Year Immunol. 1988;3:310–322. [PubMed] [Google Scholar]
  38. TRUELOVE S. C., WITTS L. J. Cortisone in ulcerative colitis; final report on a therapeutic trial. Br Med J. 1955 Oct 29;2(4947):1041–1048. doi: 10.1136/bmj.2.4947.1041. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Tamura N., Holroyd K. J., Banks T., Kirby M., Okayama H., Crystal R. G. Diversity in junctional sequences associated with the common human V gamma 9 and V delta 2 gene segments in normal blood and lung compared with the limited diversity in a granulomatous disease. J Exp Med. 1990 Jul 1;172(1):169–181. doi: 10.1084/jem.172.1.169. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Tatsumi Y., Pena J. C., Matis L., Deluca D., Bluestone J. A. Development of T cell receptor-gamma delta cells. Phenotypic and functional correlations of T cell receptor-gamma delta thymocyte maturation. J Immunol. 1993 Sep 15;151(6):3030–3041. [PubMed] [Google Scholar]
  41. Viney J., MacDonald T. T., Spencer J. Gamma/delta T cells in the gut epithelium. Gut. 1990 Aug;31(8):841–844. doi: 10.1136/gut.31.8.841. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Wen L., Peakman M., Mieli-Vergani G., Vergani D. Elevation of activated gamma delta T cell receptor bearing T lymphocytes in patients with autoimmune chronic liver disease. Clin Exp Immunol. 1992 Jul;89(1):78–82. doi: 10.1111/j.1365-2249.1992.tb06881.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Clinical and Experimental Immunology are provided here courtesy of British Society for Immunology

RESOURCES