Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1991 Nov 1;88(21):9888–9891. doi: 10.1073/pnas.88.21.9888

Identification of a limited T-cell receptor beta chain variable region repertoire associated with diabetes in the BB rat.

D P Gold 1, D Bellgrau 1
PMCID: PMC52826  PMID: 1658791

Abstract

Diabetes-prone BB rats spontaneously develop type 1 diabetes due to a T-cell-dependent destruction of insulin-producing beta-islet cells. A number of T-cell abnormalities including lymphopenia, poor cell-mediated responsiveness to alloantigen, and an absence of an RT6+ T-cell subset are associated with disease susceptibility. Our previous studies have implicated the thymic antigen-presenting cell in influencing disease potential and responsiveness to alloantigen. Since this cell type is also known to influence T-cell receptor expression in developing thymocytes, we examined the thymic and peripheral T-cell receptor beta chain variable region repertoire in diabetes-prone and diabetes-resistant rats. Our findings indicate that animals susceptible to diabetes induction have a characteristic and limited peripheral beta chain variable region repertoire that differs markedly from that expressed in the thymus.

Full text

PDF
9888

Images in this article

9889Image
on p.9889
9890Image
on p.9890
9890Image
on p.9890

Selected References

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

  1. Abe R., Vacchio M. S., Fox B., Hodes R. J. Preferential expression of the T-cell receptor V beta 3 gene by Mlsc reactive T cells. Nature. 1988 Oct 27;335(6193):827–830. doi: 10.1038/335827a0. [DOI] [PubMed] [Google Scholar]
  2. Allison J. P., McIntyre B. W., Bloch D. Tumor-specific antigen of murine T-lymphoma defined with monoclonal antibody. J Immunol. 1982 Nov;129(5):2293–2300. [PubMed] [Google Scholar]
  3. Angelillo M., Greiner D. L., Mordes J. P., Handler E. S., Nakamura N., McKeever U., Rossini A. Absence of RT6+ T cells in diabetes-prone biobreeding/Worcester rats is due to genetic and cell developmental defects. J Immunol. 1988 Dec 15;141(12):4146–4151. [PubMed] [Google Scholar]
  4. Bellgrau D., Lagarde A. C. Cytotoxic T-cell precursors with low-level CD8 in the diabetes-prone Biobreeding rat: implications for generation of an autoimmune T-cell repertoire. Proc Natl Acad Sci U S A. 1990 Jan;87(1):313–317. doi: 10.1073/pnas.87.1.313. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bellgrau D., Naji A., Silvers W. K., Markmann J. F., Barker C. F. Spontaneous diabetes in BB rats: evidence for a T cell dependent immune response defect. Diabetologia. 1982 Oct;23(4):359–364. doi: 10.1007/BF00253745. [DOI] [PubMed] [Google Scholar]
  6. Bill J., Kanagawa O., Woodland D. L., Palmer E. The MHC molecule I-E is necessary but not sufficient for the clonal deletion of V beta 11-bearing T cells. J Exp Med. 1989 Apr 1;169(4):1405–1419. doi: 10.1084/jem.169.4.1405. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  8. Chluba J., Becker A., Epplen J. T. A homologous beta-chain variable element in rat, mouse, and human T-cell receptors. Immunogenetics. 1988;28(4):292–294. doi: 10.1007/BF00345510. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. Concannon P., Wright J. A., Wright L. G., Sylvester D. R., Spielman R. S. T-cell receptor genes and insulin-dependent diabetes mellitus (IDDM): no evidence for linkage from affected sib pairs. Am J Hum Genet. 1990 Jul;47(1):45–52. [PMC free article] [PubMed] [Google Scholar]
  11. Francfort J. W., Naji A., Silvers W. K., Barker C. F. The influence of T-lymphocyte precursor cells and thymus grafts on the cellular immunodeficiencies of the BB rat. Diabetes. 1985 Nov;34(11):1134–1138. doi: 10.2337/diab.34.11.1134. [DOI] [PubMed] [Google Scholar]
  12. Fry A. M., Matis L. A. Self-tolerance alters T-cell receptor expression in an antigen-specific MHC restricted immune response. Nature. 1988 Oct 27;335(6193):830–832. doi: 10.1038/335830a0. [DOI] [PubMed] [Google Scholar]
  13. Georgiou H. M., Lagarde A. C., Bellgrau D. T cell dysfunction in the diabetes-prone BB rat. A role for thymic migrants that are not T cell precursors. J Exp Med. 1988 Jan 1;167(1):132–148. doi: 10.1084/jem.167.1.132. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Greiner D. L., Handler E. S., Nakano K., Mordes J. P., Rossini A. A. Absence of the RT-6 T cell subset in diabetes-prone BB/W rats. J Immunol. 1986 Jan;136(1):148–151. [PubMed] [Google Scholar]
  15. Greiner D. L., Mordes J. P., Handler E. S., Angelillo M., Nakamura N., Rossini A. A. Depletion of RT6.1+ T lymphocytes induces diabetes in resistant biobreeding/Worcester (BB/W) rats. J Exp Med. 1987 Aug 1;166(2):461–475. doi: 10.1084/jem.166.2.461. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Guttmann R. D., Colle E., Michel F., Seemayer T. Spontaneous diabetes mellitus syndrome in the rat. II. T lymphopenia and its association with clinical disease and pancreatic lymphocytic infiltration. J Immunol. 1983 Apr;130(4):1732–1735. [PubMed] [Google Scholar]
  17. Happ M. P., Woodland D. L., Palmer E. A third T-cell receptor beta-chain variable region gene encodes reactivity to Mls-1a gene products. Proc Natl Acad Sci U S A. 1989 Aug;86(16):6293–6296. doi: 10.1073/pnas.86.16.6293. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Hashim G., Vandenbark A. A., Gold D. P., Diamanduros T., Offner H. T cell lines specific for an immunodominant epitope of human basic protein define an encephalitogenic determinant for experimental autoimmune encephalomyelitis-resistant LOU/M rats. J Immunol. 1991 Jan 15;146(2):515–520. [PubMed] [Google Scholar]
  19. Haskins K., Kubo R., White J., Pigeon M., Kappler J., Marrack P. The major histocompatibility complex-restricted antigen receptor on T cells. I. Isolation with a monoclonal antibody. J Exp Med. 1983 Apr 1;157(4):1149–1169. doi: 10.1084/jem.157.4.1149. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Jackson R. A., Buse J. B., Rifai R., Pelletier D., Milford E. L., Carpenter C. B., Eisenbarth G. S., Williams R. M. Two genes required for diabetes in BB rats. Evidence from cyclical intercrosses and backcrosses. J Exp Med. 1984 Jun 1;159(6):1629–1636. doi: 10.1084/jem.159.6.1629. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Jackson R., Rassi N., Crump T., Haynes B., Eisenbarth G. S. The BB diabetic rat. Profound T-cell lymphocytopenia. Diabetes. 1981 Oct;30(10):887–889. doi: 10.2337/diab.30.10.887. [DOI] [PubMed] [Google Scholar]
  22. Kappler J. W., Roehm N., Marrack P. T cell tolerance by clonal elimination in the thymus. Cell. 1987 Apr 24;49(2):273–280. doi: 10.1016/0092-8674(87)90568-x. [DOI] [PubMed] [Google Scholar]
  23. Kappler J. W., Staerz U., White J., Marrack P. C. Self-tolerance eliminates T cells specific for Mls-modified products of the major histocompatibility complex. Nature. 1988 Mar 3;332(6159):35–40. doi: 10.1038/332035a0. [DOI] [PubMed] [Google Scholar]
  24. Like A. A., Biron C. A., Weringer E. J., Byman K., Sroczynski E., Guberski D. L. Prevention of diabetes in BioBreeding/Worcester rats with monoclonal antibodies that recognize T lymphocytes or natural killer cells. J Exp Med. 1986 Oct 1;164(4):1145–1159. doi: 10.1084/jem.164.4.1145. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Like A. A., Guberski D. L., Butler L. Diabetic BioBreeding/Worcester (BB/Wor) rats need not be lymphopenic. J Immunol. 1986 May 1;136(9):3254–3258. [PubMed] [Google Scholar]
  26. Like A. A., Guberski D. L., Butler L. Influence of environmental viral agents on frequency and tempo of diabetes mellitus in BB/Wor rats. Diabetes. 1991 Feb;40(2):259–262. doi: 10.2337/diab.40.2.259. [DOI] [PubMed] [Google Scholar]
  27. Like A. A., Kislauskis E., Williams R. R., Rossini A. A. Neonatal thymectomy prevents spontaneous diabetes mellitus in the BB/W rat. Science. 1982 May 7;216(4546):644–646. doi: 10.1126/science.7041259. [DOI] [PubMed] [Google Scholar]
  28. Like A. A., Rossini A. A., Guberski D. L., Appel M. C., Williams R. M. Spontaneous diabetes mellitus: reversal and prevention in the BB/W rat with antiserum to rat lymphocytes. Science. 1979 Dec 21;206(4425):1421–1423. doi: 10.1126/science.388619. [DOI] [PubMed] [Google Scholar]
  29. Like A. A., Rossini A. A. Spontaneous autoimmune diabetes mellitus in the BioBreeding/Worcester rat. Surv Synth Pathol Res. 1984;3(2):131–138. doi: 10.1159/000156921. [DOI] [PubMed] [Google Scholar]
  30. MacDonald H. R., Schneider R., Lees R. K., Howe R. C., Acha-Orbea H., Festenstein H., Zinkernagel R. M., Hengartner H. T-cell receptor V beta use predicts reactivity and tolerance to Mlsa-encoded antigens. Nature. 1988 Mar 3;332(6159):40–45. doi: 10.1038/332040a0. [DOI] [PubMed] [Google Scholar]
  31. Marrack P., Kushnir E., Kappler J. A maternally inherited superantigen encoded by a mammary tumour virus. Nature. 1991 Feb 7;349(6309):524–526. doi: 10.1038/349524a0. [DOI] [PubMed] [Google Scholar]
  32. McKeever U., Mordes J. P., Greiner D. L., Appel M. C., Rozing J., Handler E. S., Rossini A. A. Adoptive transfer of autoimmune diabetes and thyroiditis to athymic rats. Proc Natl Acad Sci U S A. 1990 Oct;87(19):7618–7622. doi: 10.1073/pnas.87.19.7618. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Morris M., Barclay A. N., Williams A. F. Analysis of T cell receptor beta chains in rat thymus, and rat C alpha and C beta sequences. Immunogenetics. 1988;27(3):174–179. doi: 10.1007/BF00346583. [DOI] [PubMed] [Google Scholar]
  34. Nakhooda A. F., Like A. A., Chappel C. I., Murray F. T., Marliss E. B. The spontaneously diabetic Wistar rat. Metabolic and morphologic studies. Diabetes. 1977 Feb;26(2):100–112. doi: 10.2337/diab.26.2.100. [DOI] [PubMed] [Google Scholar]
  35. Okada C. Y., Holzmann B., Guidos C., Palmer E., Weissman I. L. Characterization of a rat monoclonal antibody specific for a determinant encoded by the V beta 7 gene segment. Depletion of V beta 7+ T cells in mice with Mls-1a haplotype. J Immunol. 1990 May 1;144(9):3473–3477. [PubMed] [Google Scholar]
  36. Rozing J., Coolen C., Tielen F. J., Weegenaar J., Schuurman H. J., Greiner D. L., Rossini A. A. Defects in the thymic epithelial stroma of diabetes prone BB rats. Thymus. 1989;14(1-3):125–135. [PubMed] [Google Scholar]
  37. Smith L. R., Kono D. H., Theofilopoulos A. N. Complexity and sequence identification of 24 rat V beta genes. J Immunol. 1991 Jul 1;147(1):375–379. [PubMed] [Google Scholar]
  38. Sprent J., Lo D., Gao E. K., Ron Y. T cell selection in the thymus. Immunol Rev. 1988 Jan;101:173–190. doi: 10.1111/j.1600-065x.1988.tb00737.x. [DOI] [PubMed] [Google Scholar]
  39. Thomas V. A., Woda B. A., Handler E. S., Greiner D. L., Mordes J. P., Rossini A. A. Altered expression of diabetes in BB/Wor rats by exposure to viral pathogens. Diabetes. 1991 Feb;40(2):255–258. doi: 10.2337/diab.40.2.255. [DOI] [PubMed] [Google Scholar]
  40. Williams C. B., Gutman G. A. T cell receptor beta-chain genes in the rat. Availability and pattern of utilization of V gene segments differs from that in the mouse. J Immunol. 1989 Feb 1;142(3):1027–1035. [PubMed] [Google Scholar]
  41. Woda B. A., Like A. A., Padden C., McFadden M. L. Deficiency of phenotypic cytotoxic-suppressor T lymphocytes in the BB/W rat. J Immunol. 1986 Feb 1;136(3):856–859. [PubMed] [Google Scholar]
  42. Woodland D., Happ M. P., Bill J., Palmer E. Requirement for cotolerogenic gene products in the clonal deletion of I-E reactive T cells. Science. 1990 Feb 23;247(4945):964–967. doi: 10.1126/science.1968289. [DOI] [PubMed] [Google Scholar]
  43. Zipris D., Crow A. R., Delovitch T. L. Altered thymic and peripheral T-lymphocyte repertoire preceding onset of diabetes in NOD mice. Diabetes. 1991 Apr;40(4):429–435. doi: 10.2337/diab.40.4.429. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES