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. 1992 Dec 1;176(6):1785–1789. doi: 10.1084/jem.176.6.1785

Autoaggressive myocytotoxic T lymphocytes expressing an unusual gamma/delta T cell receptor

PMCID: PMC2119474  PMID: 1460433

Abstract

Polymyositis mediated by gamma/delta T cells is a unique disease in which autoaggressive T lymphocytes surround, invade, and destroy muscle fibers. Histochemically, the vast majority of muscle-infiltrating T cells in a patient with polymyositis were reactive with a pan- gamma/delta T cell receptor (TCR)-specific monoclonal antibody (TCR- delta 1+), but unlike > 90% of peripheral blood gamma/delta T cells, these lymphocytes did not react with V delta 1- or V gamma 9-specific antibodies (A13- and Ti gamma A-, respectively). Differential reactivity with two different V delta 2-specific monoclonal antibodies (BB3-/TiV-delta 2+) indicated that the infiltrating T cells express a V delta 2-containing TCR with unusual additional structural features. Using conventional and anchored polymerase chain reaction for the analysis of TCR transcripts, we found a striking predominance of one unusual V delta 2-J delta 3 recombination and one V gamma 3-J gamma 1 recombination. Both the unusual phenotype (TCR-delta 1+/A13-/Ti gamma A- /BB3-/TiV-delta 2+) and the dominance of distinct TCR transcripts are compatible with the assumption that one T cell clone, which expresses a V gamma 3-J gamma 1-C gamma 2/V delta 2-J delta 3-C delta disulfide- linked TCR, dominates among the infiltrating T cells of the polymyositis muscle specimen analyzed.

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Selected References

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  1. Casorati G., De Libero G., Lanzavecchia A., Migone N. Molecular analysis of human gamma/delta+ clones from thymus and peripheral blood. J Exp Med. 1989 Nov 1;170(5):1521–1535. doi: 10.1084/jem.170.5.1521. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. 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]
  3. Dariavach P., Lefranc M. P. First genomic sequence of the human T-cell receptor delta 2 gene (TRDV2). Nucleic Acids Res. 1989 Jun 26;17(12):4880–4880. doi: 10.1093/nar/17.12.4880. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. De Libero G., Casorati G., Giachino C., Carbonara C., Migone N., Matzinger P., Lanzavecchia A. Selection by two powerful antigens may account for the presence of the major population of human peripheral gamma/delta T cells. J Exp Med. 1991 Jun 1;173(6):1311–1322. doi: 10.1084/jem.173.6.1311. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Fagioli M., Ciccone E., Bottino C., Falini B., Grignani F., Moretta A., Moretta L., Pelicci P. G. The C gamma 1-encoded disulphide-linked and the C gamma 2-encoded nondisulphide-linked forms of the gamma/delta heterodimer use different gamma and delta variable regions. Blood. 1990 Jul 15;76(2):279–284. [PubMed] [Google Scholar]
  6. Hohlfeld R., Engel A. G., Ii K., Harper M. C. Polymyositis mediated by T lymphocytes that express the gamma/delta receptor. N Engl J Med. 1991 Mar 28;324(13):877–881. doi: 10.1056/NEJM199103283241303. [DOI] [PubMed] [Google Scholar]
  7. Kaufmann S. H. Heat shock proteins and the immune response. Immunol Today. 1990 Apr;11(4):129–136. doi: 10.1016/0167-5699(90)90050-j. [DOI] [PubMed] [Google Scholar]
  8. Keohavong P., Thilly W. G. Fidelity of DNA polymerases in DNA amplification. Proc Natl Acad Sci U S A. 1989 Dec;86(23):9253–9257. doi: 10.1073/pnas.86.23.9253. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. LeFranc M. P., Forster A., Baer R., Stinson M. A., Rabbitts T. H. Diversity and rearrangement of the human T cell rearranging gamma genes: nine germ-line variable genes belonging to two subgroups. Cell. 1986 Apr 25;45(2):237–246. doi: 10.1016/0092-8674(86)90388-0. [DOI] [PubMed] [Google Scholar]
  10. Lefranc M. P., Forster A., Rabbitts T. H. Genetic polymorphism and exon changes of the constant regions of the human T-cell rearranging gene gamma. Proc Natl Acad Sci U S A. 1986 Dec;83(24):9596–9600. doi: 10.1073/pnas.83.24.9596. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. 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]
  12. Miossec C., Faure F., Ferradini L., Roman-Roman S., Jitsukawa S., Ferrini S., Moretta A., Triebel F., Hercend T. Further analysis of the T cell receptor gamma/delta+ peripheral lymphocyte subset. The V delta 1 gene segment is expressed with either C alpha or C delta. J Exp Med. 1990 Apr 1;171(4):1171–1188. doi: 10.1084/jem.171.4.1171. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Moretta L., Ciccone E., Ferrini S., Pelicci P. G., Mingari M. C., Zeromski J., Bottino C., Grossi C., Moretta A. Molecular and cellular analysis of human T lymphocytes expressing gamma delta T-cell receptor. Immunol Rev. 1991 Apr;120:117–135. doi: 10.1111/j.1600-065x.1991.tb00590.x. [DOI] [PubMed] [Google Scholar]
  14. Ohmen J. D., Barnes P. F., Uyemura K., Lu S. Z., Grisso C. L., Modlin R. L. The T cell receptors of human gamma delta T cells reactive to Mycobacterium tuberculosis are encoded by specific V genes but diverse V-J junctions. J Immunol. 1991 Nov 15;147(10):3353–3359. [PubMed] [Google Scholar]
  15. Panchamoorthy G., McLean J., Modlin R. L., Morita C. T., Ishikawa S., Brenner M. B., Band H. A predominance of the T cell receptor V gamma 2/V delta 2 subset in human mycobacteria-responsive T cells suggests germline gene encoded recognition. J Immunol. 1991 Nov 15;147(10):3360–3369. [PubMed] [Google Scholar]
  16. Pluschke G., Ricken G., Taube H., Kroninger S., Melchers I., Peter H. H., Eichmann K., Krawinkel U. Biased T cell receptor V alpha region repertoire in the synovial fluid of rheumatoid arthritis patients. Eur J Immunol. 1991 Nov;21(11):2749–2754. doi: 10.1002/eji.1830211115. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. Quertermous T., Strauss W., Murre C., Dialynas D. P., Strominger J. L., Seidman J. G. Human T-cell gamma genes contain N segments and have marked junctional variability. Nature. 1986 Jul 10;322(6075):184–187. doi: 10.1038/322184a0. [DOI] [PubMed] [Google Scholar]
  19. Takihara Y., Tkachuk D., Michalopoulos E., Champagne E., Reimann J., Minden M., Mak T. W. Sequence and organization of the diversity, joining, and constant region genes of the human T-cell delta-chain locus. Proc Natl Acad Sci U S A. 1988 Aug;85(16):6097–6101. doi: 10.1073/pnas.85.16.6097. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Triebel F., Faure F., Mami-Chouaib F., Jitsukawa S., Griscelli A., Genevée C., Roman-Roman S., Hercend T. A novel human V delta gene expressed predominantly in the Ti gamma A fraction of gamma/delta+ peripheral lymphocytes. Eur J Immunol. 1988 Dec;18(12):2021–2027. doi: 10.1002/eji.1830181223. [DOI] [PubMed] [Google Scholar]

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