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. 1995 Feb;48(1):M46–M50. doi: 10.1136/mp.48.1.m46

Peripheral CD25 positive T lymphocytes with biased T cell receptor Vβ gene usage in autoimmune endogenous posterior uveitis

P J Tighe 1,2, J V Forrester 1,2, J Liversidge 1,2, H F Sewell 1,2
PMCID: PMC407919  PMID: 16695975

Abstract

Aims—To determine T cell receptor (TCR) Vβ gene usage in peripheral blood T lymphocytes of patients with endogenous posterior uveitis (EPU). If biased TCR variable (V) gene usage occurs in this autoimmune disease, it should be detectable in immune activated peripheral blood T cells in vivo.

Methods—Relative proportions of each Vβ gene family expressed in total peripheral blood lymphocytes (PBL) and in vivo activated (CD25+) T cells from patients with EPU and controls were determined using the anchored polymerase chain reaction (anchored PCR) in conjunction with a novel hybridisation assay. The TCR Vβ repertoires seen in these cell populations were then compared.

Results—Vβ1 usage within the CD25+ lymphocytes of patients with EPU was substantially elevated (mean ± SD 15 ±9%) compared with control CD25+ cells (3.3 ±2.4%).

Conclusions—By contrasting the repertoires of these cell populations, biased TCR Vβ gene usage was detected in patients with EPU, namely increased usage of Vβ1 in CD25+ T cells from peripheral blood of these patients. This approach of directly analysing the activated T cells in blood, using bulk PBL as an internal control, has wide applicability where specific T cell subpopulations are thought to play an important aetiopathological role.

Keywords: T cell receptor

Keywords: Vβ gene

Keywords: endogenous posterior uveitis

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Selected References

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

  1. 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]
  2. Cuccia Belvedere M., Martinetti M., de Paoli F., Mazzacane D., Redaelli C., Tafi A., Morone G. Genetic heterogeneity in uveitis. Dis Markers. 1986 Oct;4(3):243–246. [PubMed] [Google Scholar]
  3. Dick A. D., Cheng Y. F., Purdie A. T., Liversidge J., Forrester J. V. Immunocytochemical analysis of blood lymphocytes in uveitis. Eye (Lond) 1992;6(Pt 6):643–647. doi: 10.1038/eye.1992.138. [DOI] [PubMed] [Google Scholar]
  4. Feron E. J., Calder V. L., Lightman S. L. Distribution of IL-2R and CD45Ro expression on CD4+ and CD8+ T-lymphocytes in the peripheral blood of patients with posterior uveitis. Curr Eye Res. 1992;11 (Suppl):167–172. doi: 10.3109/02713689208999528. [DOI] [PubMed] [Google Scholar]
  5. Forrester J. V., Liversidge J., Dua H. S., Dick A., Harper F., McMenamin P. G. Experimental autoimmune uveoretinitis: a model system for immunointervention: a review. Curr Eye Res. 1992;11 (Suppl):33–40. doi: 10.3109/02713689208999509. [DOI] [PubMed] [Google Scholar]
  6. Friedman S. M., Tumang J. R., Crow M. K. Microbial superantigens as etiopathogenic agents in autoimmunity. Rheum Dis Clin North Am. 1993 Feb;19(1):207–222. [PubMed] [Google Scholar]
  7. Gammon G., Klotz J., Ando D., Sercarz E. E. The T cell repertoire to a multideterminant antigen. Clonal heterogeneity of the T cell response, variation between syngeneic individuals, and in vitro selection of T cell specificities. J Immunol. 1990 Mar 1;144(5):1571–1577. [PubMed] [Google Scholar]
  8. Gregerson D. S., Obritsch W. F., Fling S. P., Cameron J. D. S-antigen-specific rat T cell lines recognize peptide fragments of S-antigen and mediate experimental autoimmune uveoretinitis and pinealitis. J Immunol. 1986 Apr 15;136(8):2875–2882. [PubMed] [Google Scholar]
  9. Hashim G. A., Vandenbark A. A., Galang A. B., Diamanduros T., Carvalho E., Srinivasan J., Jones R., Vainiene M., Morrison W. J., Offner H. Antibodies specific for VB8 receptor peptide suppress experimental autoimmune encephalomyelitis. J Immunol. 1990 Jun 15;144(12):4621–4627. [PubMed] [Google Scholar]
  10. Heber-Katz E., Acha-Orbea H. The V-region disease hypothesis: evidence from autoimmune encephalomyelitis. Immunol Today. 1989 May;10(5):164–169. doi: 10.1016/0167-5699(89)90174-6. [DOI] [PubMed] [Google Scholar]
  11. Kaufman D. L., Clare-Salzler M., Tian J., Forsthuber T., Ting G. S., Robinson P., Atkinson M. A., Sercarz E. E., Tobin A. J., Lehmann P. V. Spontaneous loss of T-cell tolerance to glutamic acid decarboxylase in murine insulin-dependent diabetes. Nature. 1993 Nov 4;366(6450):69–72. doi: 10.1038/366069a0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kuppner M. C., Liversidge J., McKillop-Smith S., Lumsden L., Forrester J. V. Adhesion molecule expression in acute and fibrotic sympathetic ophthalmia. Curr Eye Res. 1993 Oct;12(10):923–934. doi: 10.3109/02713689309020399. [DOI] [PubMed] [Google Scholar]
  13. Lehmann P. V., Sercarz E. E., Forsthuber T., Dayan C. M., Gammon G. Determinant spreading and the dynamics of the autoimmune T-cell repertoire. Immunol Today. 1993 May;14(5):203–208. doi: 10.1016/0167-5699(93)90163-F. [DOI] [PubMed] [Google Scholar]
  14. Loh E. Y., Elliott J. F., Cwirla S., Lanier L. L., Davis M. M. Polymerase chain reaction with single-sided specificity: analysis of T cell receptor delta chain. Science. 1989 Jan 13;243(4888):217–220. doi: 10.1126/science.2463672. [DOI] [PubMed] [Google Scholar]
  15. Merryman C. F., Donoso L. A., Zhang X. M., Heber-Katz E., Gregerson D. S. Characterization of a new, potent, immunopathogenic epitope in S-antigen that elicits T cells expressing V beta 8 and V alpha 2-like genes. J Immunol. 1991 Jan 1;146(1):75–80. [PubMed] [Google Scholar]
  16. Navarrete C., Bottazzo G. F. In search of TCR restriction in autoreactive T cell in human autoimmunity: why is it so elusive? Clin Exp Immunol. 1993 Feb;91(2):189–192. doi: 10.1111/j.1365-2249.1993.tb05880.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Rao N. A., Naidu Y. M., Bell R., Lindsey J. W., Pararajasegaram G., Sun Y., Steinman L. Usage of T cell receptor beta-chain variable gene is highly restricted at the site of inflammation in murine autoimmune uveitis. J Immunol. 1993 Jun 15;150(12):5716–5721. [PubMed] [Google Scholar]
  18. Saiki R. K., Walsh P. S., Levenson C. H., Erlich H. A. Genetic analysis of amplified DNA with immobilized sequence-specific oligonucleotide probes. Proc Natl Acad Sci U S A. 1989 Aug;86(16):6230–6234. doi: 10.1073/pnas.86.16.6230. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Tisch R., Yang X. D., Singer S. M., Liblau R. S., Fugger L., McDevitt H. O. Immune response to glutamic acid decarboxylase correlates with insulitis in non-obese diabetic mice. Nature. 1993 Nov 4;366(6450):72–75. doi: 10.1038/366072a0. [DOI] [PubMed] [Google Scholar]
  20. Tomai M. A., Schlievert P. M., Kotb M. Distinct T-cell receptor V beta gene usage by human T lymphocytes stimulated with the streptococcal pyrogenic exotoxins and pep M5 protein. Infect Immun. 1992 Feb;60(2):701–705. doi: 10.1128/iai.60.2.701-705.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Vandenbark A. A., Hashim G., Offner H. Immunization with a synthetic T-cell receptor V-region peptide protects against experimental autoimmune encephalomyelitis. Nature. 1989 Oct 12;341(6242):541–544. doi: 10.1038/341541a0. [DOI] [PubMed] [Google Scholar]
  22. Williams W. V., Fang Q., Demarco D., VonFeldt J., Zurier R. B., Weiner D. B. Restricted heterogeneity of T cell receptor transcripts in rheumatoid synovium. J Clin Invest. 1992 Aug;90(2):326–333. doi: 10.1172/JCI115866. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Wood W. I., Gitschier J., Lasky L. A., Lawn R. M. Base composition-independent hybridization in tetramethylammonium chloride: a method for oligonucleotide screening of highly complex gene libraries. Proc Natl Acad Sci U S A. 1985 Mar;82(6):1585–1588. doi: 10.1073/pnas.82.6.1585. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. de Smet M. D., Yamamoto J. H., Mochizuki M., Gery I., Singh V. K., Shinohara T., Wiggert B., Chader G. J., Nussenblatt R. B. Cellular immune responses of patients with uveitis to retinal antigens and their fragments. Am J Ophthalmol. 1990 Aug 15;110(2):135–142. doi: 10.1016/s0002-9394(14)76981-8. [DOI] [PubMed] [Google Scholar]

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