Skip to main content
PMC home page
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1995 Jul;101(1):33–38. doi: 10.1111/j.1365-2249.1995.tb02273.x

Diverse T cell receptor beta gene usage by infiltrating T cells in the lacrimal glands of Sjögren's syndrome.

N Mizushima 1, H Kohsaka 1, K Tsubota 1, I Saito 1, N Miyasaka 1
PMCID: PMC1553308  PMID: 7621590

Abstract

Sjögren's syndrome (SS) is an autoimmune disease characterized by T cell infiltration into the salivary and lacrimal glands (LG). Previous studies on T cell receptor (TCR) usage in the minor salivary glands (SG) have yielded controversial results. We studied TCR beta gene usage of the T cells infiltrating to LG, which is the other major target organ of SS. Total RNA was extracted from fresh LG and SG biopsy samples, and peripheral blood mononuclear cells from five SS patients, and converted to cDNA. TCR V beta gene repertoire was then assessed with quantitative polymerase chain reaction (PCR) assay. Oligoclonality was studied by sequencing V-D-J junctional regions of the PCR products. The TCR V beta gene usage in LG was diverse in every patient irrespective of disease duration, and similar to that of peripheral lymphocytes from a corresponding patient. The junctional region sequences of over-expressed V beta families in LG T cells were heterogeneous. We did not find any identical clones shared by LG, SG and peripheral blood. These results showed that the infiltrating T cells in LG of SS patients are polyclonal, and LG and SG do not share the same dominant T cell clonotypes. These suggest that TCR-targeted disease manipulation may have a limited effect on SS.

Full text

PDF
33

Images in this article

34Fig. 1
on p.34

Selected References

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

  1. Adamson T. C., 3rd, Fox R. I., Frisman D. M., Howell F. V. Immunohistologic analysis of lymphoid infiltrates in primary Sjogren's syndrome using monoclonal antibodies. J Immunol. 1983 Jan;130(1):203–208. [PubMed] [Google Scholar]
  2. Choi Y. W., Kotzin B., Herron L., Callahan J., Marrack P., Kappler J. Interaction of Staphylococcus aureus toxin "superantigens" with human T cells. Proc Natl Acad Sci U S A. 1989 Nov;86(22):8941–8945. doi: 10.1073/pnas.86.22.8941. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  4. Dwyer E., Itescu S., Winchester R. Characterization of the primary structure of T cell receptor beta chains in cells infiltrating the salivary gland in the sicca syndrome of HIV-1 infection. Evidence of antigen-driven clonal selection suggested by restricted combinations of V beta J beta gene segment usage and shared somatically encoded amino acid residues. J Clin Invest. 1993 Jul;92(1):495–502. doi: 10.1172/JCI116593. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Ferradini L., Roman-Roman S., Azocar J., Michalaki H., Triebel F., Hercend T. Studies on the human T cell receptor alpha/beta variable region genes. II. Identification of four additional V beta subfamilies. Eur J Immunol. 1991 Apr;21(4):935–942. doi: 10.1002/eji.1830210412. [DOI] [PubMed] [Google Scholar]
  6. Fox R. I., Robinson C. A., Curd J. G., Kozin F., Howell F. V. Sjögren's syndrome. Proposed criteria for classification. Arthritis Rheum. 1986 May;29(5):577–585. doi: 10.1002/art.1780290501. [DOI] [PubMed] [Google Scholar]
  7. Jorgensen J. L., Esser U., Fazekas de St Groth B., Reay P. A., Davis M. M. Mapping T-cell receptor-peptide contacts by variant peptide immunization of single-chain transgenics. Nature. 1992 Jan 16;355(6357):224–230. doi: 10.1038/355224a0. [DOI] [PubMed] [Google Scholar]
  8. Kohsaka H., Chen P. P., Taniguchi A., Ollier W. E., Carson D. A. Divergent T cell receptor gamma repertoires in rheumatoid arthritis monozygotic twins. Arthritis Rheum. 1993 Feb;36(2):213–221. doi: 10.1002/art.1780360212. [DOI] [PubMed] [Google Scholar]
  9. Legras F., Martin T., Knapp A. M., Pasquali J. L. Infiltrating T cells from patients with primary Sjögren's syndrome express restricted or unrestricted T cell receptor V beta regions depending on the stage of the disease. Eur J Immunol. 1994 Jan;24(1):181–185. doi: 10.1002/eji.1830240128. [DOI] [PubMed] [Google Scholar]
  10. Lehmann P. V., Forsthuber T., Miller A., Sercarz E. E. Spreading of T-cell autoimmunity to cryptic determinants of an autoantigen. Nature. 1992 Jul 9;358(6382):155–157. doi: 10.1038/358155a0. [DOI] [PubMed] [Google Scholar]
  11. Maruyama T., Saito I., Miyake S., Hashimoto H., Sato K., Yagita H., Okumura K., Miyasaka N. A possible role of two hydrophobic amino acids in antigen recognition by synovial T cells in rheumatoid arthritis. Eur J Immunol. 1993 Sep;23(9):2059–2065. doi: 10.1002/eji.1830230903. [DOI] [PubMed] [Google Scholar]
  12. Modlin R. L., Melancon-Kaplan J., Young S. M., Pirmez C., Kino H., Convit J., Rea T. H., Bloom B. R. Learning from lesions: patterns of tissue inflammation in leprosy. Proc Natl Acad Sci U S A. 1988 Feb;85(4):1213–1217. doi: 10.1073/pnas.85.4.1213. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Mor F., Cohen I. R. Shifts in the epitopes of myelin basic protein recognized by Lewis rat T cells before, during, and after the induction of experimental autoimmune encephalomyelitis. J Clin Invest. 1993 Nov;92(5):2199–2206. doi: 10.1172/JCI116822. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Mor F., Cohen I. R. T cells in the lesion of experimental autoimmune encephalomyelitis. Enrichment for reactivities to myelin basic protein and to heat shock proteins. J Clin Invest. 1992 Dec;90(6):2447–2455. doi: 10.1172/JCI116136. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Panzara M. A., Oksenberg J. R., Steinman L. The polymerase chain reaction for detection of T-cell antigen receptor expression. Curr Opin Immunol. 1992 Apr;4(2):205–210. doi: 10.1016/0952-7915(92)90015-7. [DOI] [PubMed] [Google Scholar]
  16. Plaza A., Kono D. H., Theofilopoulos A. N. New human V beta genes and polymorphic variants. J Immunol. 1991 Dec 15;147(12):4360–4365. [PubMed] [Google Scholar]
  17. Robinson M. A. The human T cell receptor beta-chain gene complex contains at least 57 variable gene segments. Identification of six V beta genes in four new gene families. J Immunol. 1991 Jun 15;146(12):4392–4397. [PubMed] [Google Scholar]
  18. Saito I., Terauchi K., Shimuta M., Nishiimura S., Yoshino K., Takeuchi T., Tsubota K., Miyasaka N. Expression of cell adhesion molecules in the salivary and lacrimal glands of Sjogren's syndrome. J Clin Lab Anal. 1993;7(3):180–187. doi: 10.1002/jcla.1860070309. [DOI] [PubMed] [Google Scholar]
  19. St Clair E. W., Angellilo J. C., Singer K. H. Expression of cell-adhesion molecules in the salivary gland microenvironment of Sjögren's syndrome. Arthritis Rheum. 1992 Jan;35(1):62–66. doi: 10.1002/art.1780350110. [DOI] [PubMed] [Google Scholar]
  20. Sumida T., Yonaha F., Maeda T., Tanabe E., Koike T., Tomioka H., Yoshida S. T cell receptor repertoire of infiltrating T cells in lips of Sjögren's syndrome patients. J Clin Invest. 1992 Feb;89(2):681–685. doi: 10.1172/JCI115635. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Sun D., Le J., Coleclough C. Diverse T cell receptor beta chain usage by rat encephalitogenic T cells reactive to residues 68-88 of myelin basic protein. Eur J Immunol. 1993 Feb;23(2):494–498. doi: 10.1002/eji.1830230229. [DOI] [PubMed] [Google Scholar]
  22. Wucherpfennig K. W., Ota K., Endo N., Seidman J. G., Rosenzweig A., Weiner H. L., Hafler D. A. Shared human T cell receptor V beta usage to immunodominant regions of myelin basic protein. Science. 1990 May 25;248(4958):1016–1019. doi: 10.1126/science.1693015. [DOI] [PubMed] [Google Scholar]
  23. Yamamoto K., Sakoda H., Nakajima T., Kato T., Okubo M., Dohi M., Mizushima Y., Ito K., Nishioka K. Accumulation of multiple T cell clonotypes in the synovial lesions of patients with rheumatoid arthritis revealed by a novel clonality analysis. Int Immunol. 1992 Nov;4(11):1219–1223. doi: 10.1093/intimm/4.11.1219. [DOI] [PubMed] [Google Scholar]
  24. Yonaha F., Sumida T., Maeda T., Tomioka H., Koike T., Yoshida S. Restricted junctional usage of T cell receptor V beta 2 and V beta 13 genes, which are overrepresented on infiltrating T cells in the lips of patients with Sjögren's syndrome. Arthritis Rheum. 1992 Nov;35(11):1362–1367. doi: 10.1002/art.1780351118. [DOI] [PubMed] [Google Scholar]

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

RESOURCES