Skip to main content
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1993 Feb;91(2):388–390. doi: 10.1172/JCI116211

Prolongation of survival of rat cardiac allografts by T cell vaccination.

O M Shapira 1, E Mor 1, T Reshef 1, R A Pfeffermann 1, I R Cohen 1
PMCID: PMC287935  PMID: 8432846

Abstract

Administration of attenuated, activated autoimmune T lymphocytes to syngeneic mice and rats has been shown to prevent or induce remission of experimental autoimmune diseases specific for the autoimmune T cells. The process has been termed "T cell vaccination." In a recent study, T cell vaccination was done using T cells sensitized to rat alloantigens. The procedure produced a significant reduction of the mixed lymphocyte reaction (MLR) against allogeneic cells. The reduction in MLR was not specific: Vaccination with T cells specific for stimulator cells of one allotype led to a reduced MLR stimulated by cells of another allotype. The present study was undertaken to examine whether T cell vaccination can induce tolerance to transplantation antigens in vivo. We used the model of heterotopic cardiac transplantation in rats. We now report that vaccinating rats with syngeneic, activated, alloantigen-primed T lymphocytes significantly prolonged survival of rat cardiac allografts. The effect of T cell vaccination was most evident when the T cells had been obtained from rats specifically sensitized against the donor rats: Brown-Norway (BN) allografts in control Wistar rats survived 8.5 +/- 0.4 d while BN allografts survived 29.2 +/- 7.1 d in Wistar rats that had been vaccinated with Wistar anti-BN cells. Vaccination of Wistar rats with Wistar anti-hooded T cells prolonged survival of BN heart allografts to a lesser but significant degree (13.0 +/- 1.1 d). Thus, T cell vaccination of recipients can prolong survival of allografts.

Full text

PDF
389

Selected References

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

  1. Anderson L. C., Binz H., Wigzell H. Specific unresponsiveness to transplantation antigens induced by auto-immunisation with syngeneic, antigen-specific T lymphoblasts. Nature. 1976 Dec 23;264(5588):778–780. doi: 10.1038/264778a0. [DOI] [PubMed] [Google Scholar]
  2. Andersson L. C., Aguet M., Wight E., Andersson R., Binz H., Wigzell H. Induction of specific immune unresponsiveness using purified mixed leukocyte culture-activated T lymphoblasts as autoimmunogen. I. Demonstration of general validity as to species and histocompatibility barriers. J Exp Med. 1977 Oct 1;146(4):1124–1137. doi: 10.1084/jem.146.4.1124. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Baharav E., Lider O., Margalit M., Cohen I. R. A modified technique for experimental skin grafting. J Immunol Methods. 1986 Jun 10;90(1):143–144. doi: 10.1016/0022-1759(86)90395-9. [DOI] [PubMed] [Google Scholar]
  4. Ben-Nun A., Wekerle H., Cohen I. R. The rapid isolation of clonable antigen-specific T lymphocyte lines capable of mediating autoimmune encephalomyelitis. Eur J Immunol. 1981 Mar;11(3):195–199. doi: 10.1002/eji.1830110307. [DOI] [PubMed] [Google Scholar]
  5. Ben-Nun A., Wekerle H., Cohen I. R. Vaccination against autoimmune encephalomyelitis with T-lymphocyte line cells reactive against myelin basic protein. Nature. 1981 Jul 2;292(5818):60–61. doi: 10.1038/292060a0. [DOI] [PubMed] [Google Scholar]
  6. Binz H., Wigzell H. Induction of specific immune unresponsiveness with purified mixed leukocyte culture-activated T lymphoblasts as autoimmunogen. III. Proof for the existence of autoanti-idiotypic killer T cells and transfer of suppression to normal syngeneic recipients by T or B lymphocytes. J Exp Med. 1978 Jan 1;147(1):63–76. doi: 10.1084/jem.147.1.63. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Binz H., Wigzell H. Specific transplantation tolerance induced by autoimmunization against the individual's own, naturally occurring idiotypic, antigen-binding receptors. J Exp Med. 1976 Dec 1;144(6):1438–1457. doi: 10.1084/jem.144.6.1438. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Binz H., Wigzell H. Successful induction of specific tolerance to transplantation antigens using autoimmunisation against the recipient's own natural antibodies. Nature. 1976 Jul 22;262(5566):294–295. doi: 10.1038/262294a0. [DOI] [PubMed] [Google Scholar]
  9. Cohen I. R. Regulation of autoimmune disease physiological and therapeutic. Immunol Rev. 1986 Dec;94:5–21. doi: 10.1111/j.1600-065x.1986.tb01161.x. [DOI] [PubMed] [Google Scholar]
  10. Lagaaij E. L., Hennemann I. P., Ruigrok M., de Haan M. W., Persijn G. G., Termijtelen A., Hendricks G. F., Weimar W., Claas F. H., van Rood J. J. Effect of one-HLA-DR-antigen-matched and completely HLA-DR-mismatched blood transfusions on survival of heart and kidney allografts. N Engl J Med. 1989 Sep 14;321(11):701–705. doi: 10.1056/NEJM198909143211101. [DOI] [PubMed] [Google Scholar]
  11. Lider O., Karin N., Shinitzky M., Cohen I. R. Therapeutic vaccination against adjuvant arthritis using autoimmune T cells treated with hydrostatic pressure. Proc Natl Acad Sci U S A. 1987 Jul;84(13):4577–4580. doi: 10.1073/pnas.84.13.4577. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Lider O., Reshef T., Beraud E., Ben-Nun A., Cohen I. R. Anti-idiotypic network induced by T cell vaccination against experimental autoimmune encephalomyelitis. Science. 1988 Jan 8;239(4836):181–183. doi: 10.1126/science.2447648. [DOI] [PubMed] [Google Scholar]
  13. Lohse A. W., Mor E., Reshef T., Meyer zum Büschenfelde K. H., Cohen I. R. Inhibition of the mixed lymphocyte reaction by T cell vaccination. Eur J Immunol. 1990 Nov;20(11):2521–2524. doi: 10.1002/eji.1830201126. [DOI] [PubMed] [Google Scholar]
  14. Lohse A. W., Mor F., Karin N., Cohen I. R. Control of experimental autoimmune encephalomyelitis by T cells responding to activated T cells. Science. 1989 May 19;244(4906):820–822. doi: 10.1126/science.2471264. [DOI] [PubMed] [Google Scholar]
  15. Maron R., Zerubavel R., Friedman A., Cohen I. R. T lymphocyte line specific for thyroglobulin produces or vaccinates against autoimmune thyroiditis in mice. J Immunol. 1983 Nov;131(5):2316–2322. [PubMed] [Google Scholar]
  16. Mor F., Lohse A. W., Karin N., Cohen I. R. Clinical modeling of T cell vaccination against autoimmune diseases in rats. Selection of antigen-specific T cells using a mitogen. J Clin Invest. 1990 May;85(5):1594–1598. doi: 10.1172/JCI114610. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Offner H., Vainiene M., Gold D. P., Morrison W. J., Wang R. Y., Hashim G. A., Vandenbark A. A. Protection against experimental encephalomyelitis. Idiotypic autoregulation induced by a nonencephalitogenic T cell clone expressing a cross-reactive T cell receptor V gene. J Immunol. 1991 Jun 15;146(12):4165–4172. [PubMed] [Google Scholar]
  18. Ono K., Lindsey E. S. Improved technique of heart transplantation in rats. J Thorac Cardiovasc Surg. 1969 Feb;57(2):225–229. [PubMed] [Google Scholar]
  19. Sun D., Qin Y., Chluba J., Epplen J. T., Wekerle H. Suppression of experimentally induced autoimmune encephalomyelitis by cytolytic T-T cell interactions. Nature. 1988 Apr 28;332(6167):843–845. doi: 10.1038/332843a0. [DOI] [PubMed] [Google Scholar]
  20. 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]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES