Skip to main content
NCBI home page
Infection and Immunity logoLink to Infection and Immunity
. 1996 Apr;64(4):1391–1399. doi: 10.1128/iai.64.4.1391-1399.1996

Changes in the peripheral blood T-Cell receptor V beta repertoire in vivo and in vitro during shigellosis.

D Islam 1, B Wretlind 1, A A Lindberg 1, B Christensson 1
PMCID: PMC173931  PMID: 8606106

Abstract

A sequential activation of T cells in peripheral blood during shigello sis has been observer (D. Islam, P.K. Bradham, A. A. Lindberg, and B. Christensson, Infect. Immun 63:2941-2949, 1995). To further investigate the cellular response during the course of Shigella infection, changes in the T-cell receptor (TCR) repertoire in the subsets in blood in patients during shigellosis was that Shigella antigens may modulate the function of T cells carrying TCRs capable of recognizing Shigella-specific epitopes or superantigens. Such a selective preference for T cells expressing certain TCR Vbeta types could lead to the expansion or deletion of these T cells. In the present study of 27 adult male Bangladeshi patients with dysentery (14 cases caused by Shigella Dysenteriae 1 and 13 cases caused by Shigella flexneri), the changes in the TCR Vbeta repertoire of peripheral blood CD4+ and CD8+ T-cell subsets have been analyzed with a panel of nine anti-Vbeta monoclonal antibodies by flow cytometry. Twenty healthy males from Bangladesh and 20 healthy males from Sweden served as controls. Compared with the Bangladeshi controls, the patients had an increased frequency of CD4+T cells expression Vbeta2, Vbeta3, and Vbeta17, with a maximum at day 7 after the onset of disease. The frequency of CD4+T cells expressing Vbeta5.1 was increased only in patients with S. flexneri infection. Peripheral blood T cells from Shigella-infected patients also responded to in vitro stimulation in a TCR Vbeta-specific manner. Stimulation with heat-killed S. dysenteriae 1 and Shiga toxin enhanced the frequency of cells expressing Vbeta2, Vbeta3, Vbeta5.1, Vbeta13.6, and Vbeta17, especially in samples obtained at day 7. The enhanced frequency of cells expressing Vbeta2, Vbeta3, Vbeta5.1, and Vbeta17 found both in in vivo and in vitro could suggest that in shigellosis antigens or superantigens are presented to the immune system and preferentially activate certain TCR Vbeta types in T-cell subsets. The kinetics of the change in the TCR Vbeta repertoire in blood during shigellosis may indicate that following local activation, the antigen activated T cells can be retrieved in the blood and restimulated in vitro. If confirmed by parallel analysis of T cells in the gut and blood by TCR sequence analysis, the possibility suggested by our findings would facilitate further analysis of the role of cell-mediated immune responses in the pathogenesis of and protection against Shigella infection.

Full Text

The Full Text of this article is available as a PDF (401.0 KB).

Selected References

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

  1. Abe J., Kotzin B. L., Jujo K., Melish M. E., Glode M. P., Kohsaka T., Leung D. Y. Selective expansion of T cells expressing T-cell receptor variable regions V beta 2 and V beta 8 in Kawasaki disease. Proc Natl Acad Sci U S A. 1992 May 1;89(9):4066–4070. doi: 10.1073/pnas.89.9.4066. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Abe J., Kotzin B. L., Meissner C., Melish M. E., Takahashi M., Fulton D., Romagne F., Malissen B., Leung D. Y. Characterization of T cell repertoire changes in acute Kawasaki disease. J Exp Med. 1993 Mar 1;177(3):791–796. doi: 10.1084/jem.177.3.791. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Acha-Orbea H. Bacterial and viral superantigens: roles in autoimmunity? Ann Rheum Dis. 1993 Mar;52 (Suppl 1):S6–16. doi: 10.1136/ard.52.suppl_1.s6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Acha-Orbea H. Roles of superantigens in microbial infections? Res Immunol. 1993 Mar-Apr;144(3):198–222. doi: 10.1016/0923-2494(93)80118-i. [DOI] [PubMed] [Google Scholar]
  5. Akolkar P. N., Chirmule N., Gulwani-Akolkar B., Pahwa S., Kalyanaraman V. S., Pergolizzi R., Macphail S., Silver J. V beta-specific activation of T cells by the HIV glycoprotein gp 160. Scand J Immunol. 1995 May;41(5):487–498. doi: 10.1111/j.1365-3083.1995.tb03597.x. [DOI] [PubMed] [Google Scholar]
  6. Beckman E. M., Porcelli S. A., Morita C. T., Behar S. M., Furlong S. T., Brenner M. B. Recognition of a lipid antigen by CD1-restricted alpha beta+ T cells. Nature. 1994 Dec 15;372(6507):691–694. doi: 10.1038/372691a0. [DOI] [PubMed] [Google Scholar]
  7. Choi Y., Kappler J. W., Marrack P. A superantigen encoded in the open reading frame of the 3' long terminal repeat of mouse mammary tumour virus. Nature. 1991 Mar 21;350(6315):203–207. doi: 10.1038/350203a0. [DOI] [PubMed] [Google Scholar]
  8. Chou Y. K., Henderikx P., Vainiene M., Whitham R., Bourdette D., Chou C. H., Hashim G., Offner H., Vandenbark A. A. Specificity of human T cell clones reactive to immunodominant epitopes of myelin basic protein. J Neurosci Res. 1991 Feb;28(2):280–290. doi: 10.1002/jnr.490280215. [DOI] [PubMed] [Google Scholar]
  9. D'Orazio J. A., Burke G. W., Stein-Streilein J. Staphylococcal enterotoxin B activates purified NK cells to secrete IFN-gamma but requires T lymphocytes to augment NK cytotoxicity. J Immunol. 1995 Feb 1;154(3):1014–1023. [PubMed] [Google Scholar]
  10. Dadaglio G., Garcia S., Montagnier L., Gougeon M. L. Selective anergy of V beta 8+ T cells in human immunodeficiency virus-infected individuals. J Exp Med. 1994 Feb 1;179(2):413–424. doi: 10.1084/jem.179.2.413. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Friedman S. M., Crow M. K., Tumang J. R., Tumang M., Xu Y. Q., Hodtsev A. S., Cole B. C., Posnett D. N. Characterization of human T cells reactive with the Mycoplasma arthritidis-derived superantigen (MAM): generation of a monoclonal antibody against V beta 17, the T cell receptor gene product expressed by a large fraction of MAM-reactive human T cells. J Exp Med. 1991 Oct 1;174(4):891–900. doi: 10.1084/jem.174.4.891. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Fält I. C., Schweda E. K., Weintraub A., Sturm S., Timmis K. N., Lindberg A. A. Expression of the Shigella dysenteriae type-1 lipopolysaccharide repeating unit in Escherichia coli K12/Shigella dysenteriae type-1 hybrids. Eur J Biochem. 1993 Apr 1;213(1):573–581. doi: 10.1111/j.1432-1033.1993.tb17796.x. [DOI] [PubMed] [Google Scholar]
  13. Galelli A., Delcourt M., Wagner M. C., Peumans W., Truffa-Bachi P. Selective expansion followed by profound deletion of mature V beta 8.3+ T cells in vivo after exposure to the superantigenic lectin Urtica dioica agglutinin. J Immunol. 1995 Mar 15;154(6):2600–2611. [PubMed] [Google Scholar]
  14. Geluk A., Fu X. T., van Meijgaarden K. E., Jansen Y. Y., De Vries R. R., Karr R. W., Ottenhoff T. H. T cell receptor and peptide-contacting residues in the HLA-DR17(3) beta 1 chain. Eur J Immunol. 1994 Dec;24(12):3241–3244. doi: 10.1002/eji.1830241251. [DOI] [PubMed] [Google Scholar]
  15. Germain R. N. MHC-dependent antigen processing and peptide presentation: providing ligands for T lymphocyte activation. Cell. 1994 Jan 28;76(2):287–299. doi: 10.1016/0092-8674(94)90336-0. [DOI] [PubMed] [Google Scholar]
  16. Grunewald J., Janson C. H., Eklund A., Ohrn M., Olerup O., Persson U., Wigzell H. Restricted V alpha 2.3 gene usage by CD4+ T lymphocytes in bronchoalveolar lavage fluid from sarcoidosis patients correlates with HLA-DR3. Eur J Immunol. 1992 Jan;22(1):129–135. doi: 10.1002/eji.1830220120. [DOI] [PubMed] [Google Scholar]
  17. Grunewald J., Olerup O., Persson U., Ohrn M. B., Wigzell H., Eklund A. T-cell receptor variable region gene usage by CD4+ and CD8+ T cells in bronchoalveolar lavage fluid and peripheral blood of sarcoidosis patients. Proc Natl Acad Sci U S A. 1994 May 24;91(11):4965–4969. doi: 10.1073/pnas.91.11.4965. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. 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]
  19. Herman A., Kappler J. W., Marrack P., Pullen A. M. Superantigens: mechanism of T-cell stimulation and role in immune responses. Annu Rev Immunol. 1991;9:745–772. doi: 10.1146/annurev.iy.09.040191.003525. [DOI] [PubMed] [Google Scholar]
  20. Hodara V. L., Jeddi-Tehrani M., Grunewald J., Andersson R., Scarlatti G., Esin S., Holmberg V., Libonatti O., Wigzell H. HIV infection leads to differential expression of T-cell receptor V beta genes in CD4+ and CD8+ T cells. AIDS. 1993 May;7(5):633–638. doi: 10.1097/00002030-199305000-00004. [DOI] [PubMed] [Google Scholar]
  21. Howell M. D., Diveley J. P., Lundeen K. A., Esty A., Winters S. T., Carlo D. J., Brostoff S. W. Limited T-cell receptor beta-chain heterogeneity among interleukin 2 receptor-positive synovial T cells suggests a role for superantigen in rheumatoid arthritis. Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10921–10925. doi: 10.1073/pnas.88.23.10921. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Islam D., Bardhan P. K., Lindberg A. A., Christensson B. Shigella infection induces cellular activation of T and B cells and distinct species-related changes in peripheral blood lymphocyte subsets during the course of the disease. Infect Immun. 1995 Aug;63(8):2941–2949. doi: 10.1128/iai.63.8.2941-2949.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Islam D., Lindberg A. A., Christensson B. Peripheral blood cell preparation influences the level of expression of leukocyte cell surface markers as assessed with quantitative multicolor flow cytometry. Cytometry. 1995 Jun 15;22(2):128–134. doi: 10.1002/cyto.990220208. [DOI] [PubMed] [Google Scholar]
  24. Islam D., Wretlind B., Ryd M., Lindberg A. A., Christensson B. Immunoglobulin subclass distribution and dynamics of Shigella-specific antibody responses in serum and stool samples in shigellosis. Infect Immun. 1995 May;63(5):2054–2061. doi: 10.1128/iai.63.5.2054-2061.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Janeway C. A., Jr, Dianzani U., Portoles P., Rath S., Reich E. P., Rojo J., Yagi J., Murphy D. B. Cross-linking and conformational change in T-cell receptors: role in activation and in repertoire selection. Cold Spring Harb Symp Quant Biol. 1989;54(Pt 2):657–666. doi: 10.1101/sqb.1989.054.01.077. [DOI] [PubMed] [Google Scholar]
  26. Kappler J., Kotzin B., Herron L., Gelfand E. W., Bigler R. D., Boylston A., Carrel S., Posnett D. N., Choi Y., Marrack P. V beta-specific stimulation of human T cells by staphylococcal toxins. Science. 1989 May 19;244(4906):811–813. doi: 10.1126/science.2524876. [DOI] [PubMed] [Google Scholar]
  27. Kawabe Y., Ochi A. Selective anergy of V beta 8+,CD4+ T cells in Staphylococcus enterotoxin B-primed mice. J Exp Med. 1990 Oct 1;172(4):1065–1070. doi: 10.1084/jem.172.4.1065. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Marrack P., Kappler J. The staphylococcal enterotoxins and their relatives. Science. 1990 May 11;248(4956):705–711. doi: 10.1126/science.2185544. [DOI] [PubMed] [Google Scholar]
  29. Mattern T., Thanhäuser A., Reiling N., Toellner K. M., Duchrow M., Kusumoto S., Rietschel E. T., Ernst M., Brade H., Flad H. D. Endotoxin and lipid A stimulate proliferation of human T cells in the presence of autologous monocytes. J Immunol. 1994 Oct 1;153(7):2996–3004. [PubMed] [Google Scholar]
  30. McCormack J. E., Callahan J. E., Kappler J., Marrack P. C. Profound deletion of mature T cells in vivo by chronic exposure to exogenous superantigen. J Immunol. 1993 May 1;150(9):3785–3792. [PubMed] [Google Scholar]
  31. Meinl E., Weber F., Drexler K., Morelle C., Ott M., Saruhan-Direskeneli G., Goebels N., Ertl B., Jechart G., Giegerich G. Myelin basic protein-specific T lymphocyte repertoire in multiple sclerosis. Complexity of the response and dominance of nested epitopes due to recruitment of multiple T cell clones. J Clin Invest. 1993 Dec;92(6):2633–2643. doi: 10.1172/JCI116879. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Moyer M. P., Dixon P. S., Rothman S. W., Brown J. E. Cytotoxicity of Shiga toxin for primary cultures of human colonic and ileal epithelial cells. Infect Immun. 1987 Jun;55(6):1533–1535. doi: 10.1128/iai.55.6.1533-1535.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Oksenberg J. R., Stuart S., Begovich A. B., Bell R. B., Erlich H. A., Steinman L., Bernard C. C. Limited heterogeneity of rearranged T-cell receptor V alpha transcripts in brains of multiple sclerosis patients. Nature. 1990 May 24;345(6273):344–346. doi: 10.1038/345344a0. [DOI] [PubMed] [Google Scholar]
  34. Paliard X., West S. G., Lafferty J. A., Clements J. R., Kappler J. W., Marrack P., Kotzin B. L. Evidence for the effects of a superantigen in rheumatoid arthritis. Science. 1991 Jul 19;253(5017):325–329. doi: 10.1126/science.1857971. [DOI] [PubMed] [Google Scholar]
  35. Pietra B. A., De Inocencio J., Giannini E. H., Hirsch R. TCR V beta family repertoire and T cell activation markers in Kawasaki disease. J Immunol. 1994 Aug 15;153(4):1881–1888. [PubMed] [Google Scholar]
  36. Ramakrishnan N. S., Grunewald J., Janson C. H., Wigzell H. Nearly identical T-cell receptor V-gene usage at birth in two cohorts of distinctly different ethnic origin: influence of environment in the final maturation in the adult. Scand J Immunol. 1992 Jul;36(1):71–78. doi: 10.1111/j.1365-3083.1992.tb02942.x. [DOI] [PubMed] [Google Scholar]
  37. Raqib R., Reinholt F. P., Bardhan P. K., Kärnell A., Lindberg A. A. Immunopathological patterns in the rectal mucosa of patients with shigellosis: expression of HLA-DR antigens and T-lymphocyte subsets. APMIS. 1994 May;102(5):371–380. doi: 10.1111/j.1699-0463.1994.tb04886.x. [DOI] [PubMed] [Google Scholar]
  38. Raqib R., Wretlind B., Andersson J., Lindberg A. A. Cytokine secretion in acute shigellosis is correlated to disease activity and directed more to stool than to plasma. J Infect Dis. 1995 Feb;171(2):376–384. doi: 10.1093/infdis/171.2.376. [DOI] [PubMed] [Google Scholar]
  39. Romagné F., Besnardeau L., Malissen B. A versatile method to produce antibodies to human T cell receptor V beta segments: frequency determination of human V beta 2+ T cells that react with toxic-shock syndrome toxin-1. Eur J Immunol. 1992 Oct;22(10):2749–2752. doi: 10.1002/eji.1830221043. [DOI] [PubMed] [Google Scholar]
  40. Shimoda S., Nakamura M., Ishibashi H., Hayashida K., Niho Y. HLA DRB4 0101-restricted immunodominant T cell autoepitope of pyruvate dehydrogenase complex in primary biliary cirrhosis: evidence of molecular mimicry in human autoimmune diseases. J Exp Med. 1995 May 1;181(5):1835–1845. doi: 10.1084/jem.181.5.1835. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Springer T. A. Adhesion receptors of the immune system. Nature. 1990 Aug 2;346(6283):425–434. doi: 10.1038/346425a0. [DOI] [PubMed] [Google Scholar]
  42. Springer T. A. Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm. Cell. 1994 Jan 28;76(2):301–314. doi: 10.1016/0092-8674(94)90337-9. [DOI] [PubMed] [Google Scholar]
  43. Tanaka Y., Morita C. T., Tanaka Y., Nieves E., Brenner M. B., Bloom B. R. Natural and synthetic non-peptide antigens recognized by human gamma delta T cells. Nature. 1995 May 11;375(6527):155–158. doi: 10.1038/375155a0. [DOI] [PubMed] [Google Scholar]
  44. Toft P., Lillevang S. T., Tønnesen E., Svendsen P., Höhndorf K. Redistribution of lymphocytes following E. coli sepsis. Scand J Immunol. 1993 Dec;38(6):541–545. doi: 10.1111/j.1365-3083.1993.tb03238.x. [DOI] [PubMed] [Google Scholar]
  45. Udhayakumar V., Anyona D., Kariuki S., Shi Y. P., Bloland P. B., Branch O. H., Weiss W., Nahlen B. L., Kaslow D. C., Lal A. A. Identification of T and B cell epitopes recognized by humans in the C-terminal 42-kDa domain of the Plasmodium falciparum merozoite surface protein (MSP)-1. J Immunol. 1995 Jun 1;154(11):6022–6030. [PubMed] [Google Scholar]
  46. Valitutti S., Müller S., Cella M., Padovan E., Lanzavecchia A. Serial triggering of many T-cell receptors by a few peptide-MHC complexes. Nature. 1995 May 11;375(6527):148–151. doi: 10.1038/375148a0. [DOI] [PubMed] [Google Scholar]
  47. de Silva D. G., Mendis L. N., Sheron N., Alexander G. J., Candy D. C., Chart H., Rowe B. Concentrations of interleukin 6 and tumour necrosis factor in serum and stools of children with Shigella dysenteriae 1 infection. Gut. 1993 Feb;34(2):194–198. doi: 10.1136/gut.34.2.194. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES