Skip to main content
PMC home page
Immunology logoLink to Immunology
. 1997 Aug;91(4):520–528. doi: 10.1046/j.1365-2567.1997.00306.x

The characterization of testicular cell (TC)-specific T-cell clones induced by intratesticular Listeria monocytogenes infection: TC-specific T cells with atypical cytokine profile transfer orchitis.

G Matsuzaki 1, K H Sonoda 1, A Mukasa 1, H Yamada 1, T Nakamura 1, H Ikebe 1, S Hamano 1, K Nomoto 1
PMCID: PMC1363870  PMID: 9378489

Abstract

A unilateral infection of Listeria monocytogenes into the testis of mice induces not only Listeria-specific T cells but also autoreactive T cells that can transfer experimental autoimmune orchitis (EAO) into naive mice. To investigate the characteristics of the autoreactive T cells, we established six testicular cell (TC)-specific T-cell clones from the spleen of the intratesticularly infected mice. All the clones expressed CD4 and T-cell receptor (TCR) alpha beta, and four of the six clones expressed V beta 8. They showed proliferative response to TC in the presence of syngeneic spleen antigen-presenting cells, but did not cross-react to Listeria antigen (Ag). They produced interferon-gamma (IFN-gamma) when stimulated with TC, but interleukin-2 (IL-2), IL-4 and IL-10 were undetectable. IL-2 production was not detected even when they were restimulated with TC after a 10-day resting culture without Ag and IL-2, although they proliferated in the restimulation culture. Even in the presence of anti-IL-2 mAb, the TC-specific T-cell clones showed proliferative response against TC. The observations indicate that the TC-specific IFN-gamma-producing T cells proliferate in the absence of autocrine. Both intravenous and intratesticular injection of these clones transferred EAO in syngeneic naive mice. These results suggest that L. monocytogenes infection in the testis induces autoreactive orchitogenic CD4+ T cells without cross-reactivity to bacterial Ag. Furthermore, these data demonstrate that CD4+ T cells with an atypical cytokine profile can efficiently cause EAO.

Full text

PDF
520

Images in this article

525Figure 3
on p.525
527Figure 7
on p.527

Selected References

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

  1. Alderson M. R., Armitage R. J., Maraskovsky E., Tough T. W., Roux E., Schooley K., Ramsdell F., Lynch D. H. Fas transduces activation signals in normal human T lymphocytes. J Exp Med. 1993 Dec 1;178(6):2231–2235. doi: 10.1084/jem.178.6.2231. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Asano M., Toda M., Sakaguchi N., Sakaguchi S. Autoimmune disease as a consequence of developmental abnormality of a T cell subpopulation. J Exp Med. 1996 Aug 1;184(2):387–396. doi: 10.1084/jem.184.2.387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bellgrau D., Gold D., Selawry H., Moore J., Franzusoff A., Duke R. C. A role for CD95 ligand in preventing graft rejection. Nature. 1995 Oct 19;377(6550):630–632. doi: 10.1038/377630a0. [DOI] [PubMed] [Google Scholar]
  4. Fournel S., Genestier L., Robinet E., Flacher M., Revillard J. P. Human T cells require IL-2 but not G1/S transition to acquire susceptibility to Fas-mediated apoptosis. J Immunol. 1996 Nov 15;157(10):4309–4315. [PubMed] [Google Scholar]
  5. Gianani R., Sarvetnick N. Viruses, cytokines, antigens, and autoimmunity. Proc Natl Acad Sci U S A. 1996 Mar 19;93(6):2257–2259. doi: 10.1073/pnas.93.6.2257. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Goverman J., Woods A., Larson L., Weiner L. P., Hood L., Zaller D. M. Transgenic mice that express a myelin basic protein-specific T cell receptor develop spontaneous autoimmunity. Cell. 1993 Feb 26;72(4):551–560. doi: 10.1016/0092-8674(93)90074-z. [DOI] [PubMed] [Google Scholar]
  7. Itoh M., Hiramine C., Hojo K. A new murine model of autoimmune orchitis induced by immunization with viable syngeneic testicular germ cells alone. I. Immunological and histological studies. Clin Exp Immunol. 1991 Jan;83(1):137–142. doi: 10.1111/j.1365-2249.1991.tb05603.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Kingsley G., Sieper J. Current perspectives in reactive arthritis. Immunol Today. 1993 Aug;14(8):387–391. doi: 10.1016/0167-5699(93)90139-C. [DOI] [PubMed] [Google Scholar]
  9. Klas C., Debatin K. M., Jonker R. R., Krammer P. H. Activation interferes with the APO-1 pathway in mature human T cells. Int Immunol. 1993 Jun;5(6):625–630. doi: 10.1093/intimm/5.6.625. [DOI] [PubMed] [Google Scholar]
  10. Kneitz B., Herrmann T., Yonehara S., Schimpl A. Normal clonal expansion but impaired Fas-mediated cell death and anergy induction in interleukin-2-deficient mice. Eur J Immunol. 1995 Sep;25(9):2572–2577. doi: 10.1002/eji.1830250925. [DOI] [PubMed] [Google Scholar]
  11. Mukasa A., Hiromatsu K., Matsuzaki G., O'Brien R., Born W., Nomoto K. Bacterial infection of the testis leading to autoaggressive immunity triggers apparently opposed responses of alpha beta and gamma delta T cells. J Immunol. 1995 Aug 15;155(4):2047–2056. [PubMed] [Google Scholar]
  12. Mukasa A., Itoh M., Tokunaga Y., Hiramine C., Hojo K. Inhibition of a novel model of murine experimental autoimmune orchitis by intravenous administration with a soluble testicular antigen: participation of CD8+ regulatory T cells. Clin Immunol Immunopathol. 1992 Feb;62(2):210–219. doi: 10.1016/0090-1229(92)90074-x. [DOI] [PubMed] [Google Scholar]
  13. Osman G. E., Toda M., Kanagawa O., Hood L. E. Characterization of the T cell receptor repertoire causing collagen arthritis in mice. J Exp Med. 1993 Feb 1;177(2):387–395. doi: 10.1084/jem.177.2.387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Rathmell J. C., Townsend S. E., Xu J. C., Flavell R. A., Goodnow C. C. Expansion or elimination of B cells in vivo: dual roles for CD40- and Fas (CD95)-ligands modulated by the B cell antigen receptor. Cell. 1996 Oct 18;87(2):319–329. doi: 10.1016/s0092-8674(00)81349-5. [DOI] [PubMed] [Google Scholar]
  15. Rizzo L. V., Silver P., Wiggert B., Hakim F., Gazzinelli R. T., Chan C. C., Caspi R. R. Establishment and characterization of a murine CD4+ T cell line and clone that induce experimental autoimmune uveoretinitis in B10.A mice. J Immunol. 1996 Feb 15;156(4):1654–1660. [PubMed] [Google Scholar]
  16. Rose N. R., Neumann D. A., Herskowitz A. Autoimmune myocarditis: concepts and questions. Immunol Today. 1991 Aug;12(8):253–255. doi: 10.1016/0167-5699(91)90118-D. [DOI] [PubMed] [Google Scholar]
  17. Sanui H., Yoshida S., Himeno K., Nomoto K. Experimental allergic orchitis induced by unilateral intratesticular bacterial infection in guinea-pigs. Immunology. 1983 May;49(1):45–51. [PMC free article] [PubMed] [Google Scholar]
  18. Song F., Matsuzaki G., Mitsuyama M., Nomoto K. Differential effects of viable and killed bacteria on IL-12 expression of macrophages. J Immunol. 1996 Apr 15;156(8):2979–2984. [PubMed] [Google Scholar]
  19. Song F., Matsuzaki G., Mitsuyama M., Nomoto K. In vitro generation of IFN-gamma-producing Listeria-specific T cells is dependent on IFN-gamma production by non-NK cells. Cell Immunol. 1995 Feb;160(2):211–216. doi: 10.1016/0008-8749(95)80030-m. [DOI] [PubMed] [Google Scholar]
  20. Sonoda K., Mukasa A., Matsuzaki G., Nomoto K. The induction of renal autoantigen-specific T cells by a local Listeria monocytogenes infection. Immunology. 1995 Oct;86(2):190–198. [PMC free article] [PubMed] [Google Scholar]
  21. Taguchi O., Takahashi T. Administration of anti-interleukin-2 receptor alpha antibody in vivo induces localized autoimmune disease. Eur J Immunol. 1996 Jul;26(7):1608–1612. doi: 10.1002/eji.1830260730. [DOI] [PubMed] [Google Scholar]
  22. Trentham D. E., Townes A. S., Kang A. H. Autoimmunity to type II collagen an experimental model of arthritis. J Exp Med. 1977 Sep 1;146(3):857–868. doi: 10.1084/jem.146.3.857. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Tung K. S., Leong C., McCarty T. Pathogenesis of experimental allergic orchitis. III. T lymphocyte requirement in local adoptive transfer by peritoneal exudate cells. J Immunol. 1977 May;118(5):1774–1779. [PubMed] [Google Scholar]
  24. Tung K. S., Yule T. D., Mahi-Brown C. A., Listrom M. B. Distribution of histopathology and Ia positive cells in actively induced and passively transferred experimental autoimmune orchitis. J Immunol. 1987 Feb 1;138(3):752–759. [PubMed] [Google Scholar]
  25. Wacker W. B., Donoso L. A., Kalsow C. M., Yankeelov J. A., Jr, Organisciak D. T. Experimental allergic uveitis. Isolation, characterization, and localization of a soluble uveitopathogenic antigen from bovine retina. J Immunol. 1977 Dec;119(6):1949–1958. [PubMed] [Google Scholar]
  26. Wekerle H., Begemann M. In vitro induction of experimental autoimmune orchitis: characterization of a primary T lymhocyte response against testicular self antigens. Eur J Immunol. 1978 May;8(5):294–302. doi: 10.1002/eji.1830080503. [DOI] [PubMed] [Google Scholar]
  27. Yule T. D., Tung K. S. Experimental autoimmune orchitis induced by testis and sperm antigen-specific T cell clones: an important pathogenic cytokine is tumor necrosis factor. Endocrinology. 1993 Sep;133(3):1098–1107. doi: 10.1210/endo.133.3.8103448. [DOI] [PubMed] [Google Scholar]
  28. Zaller D. M., Osman G., Kanagawa O., Hood L. Prevention and treatment of murine experimental allergic encephalomyelitis with T cell receptor V beta-specific antibodies. J Exp Med. 1990 Jun 1;171(6):1943–1955. doi: 10.1084/jem.171.6.1943. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Zamvil S. S., Steinman L. The T lymphocyte in experimental allergic encephalomyelitis. Annu Rev Immunol. 1990;8:579–621. doi: 10.1146/annurev.iy.08.040190.003051. [DOI] [PubMed] [Google Scholar]

Articles from Immunology are provided here courtesy of British Society for Immunology

RESOURCES