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. 1992 Nov;66(11):6541–6546. doi: 10.1128/jvi.66.11.6541-6546.1992

T cells expressing the gamma delta T-cell receptor potentiate coxsackievirus B3-induced myocarditis.

S A Huber 1, A Moraska 1, M Choate 1
PMCID: PMC240148  PMID: 1328680

Abstract

Initial studies determined whether intraperitoneal (i.p.) injection of BALB/c mice with 0.1, 1.0, and 10 mg of adriamycin (a cardiotoxic anthracycline antibiotic) for times ranging between 1 and 9 weeks prior to i.p. injection of 10(5) PFU of coxsackievirus B3 (CVB3) would alter the severity of virus-induced myocarditis. Prior adriamycin exposure enhanced pathogenicity of a poorly pathogenic CVB3 variant (H310A1) but had no effect on myocarditis produced by the pathogenic variant (H3). Cardiac virus concentrations were equivalent in H3- and H310A1-infected mice irrespective of adriamycin treatment. BALB/c mice treated with either 0.1 ml of complete Freund's adjuvant (CFA), 10 mg of adriamycin, or 10(5) PFU of H3 and H310A1 i.p. developed cytolytic Thy 1.2+ lymphocytes (CTL) to H3-infected myocytes 7 days later. CFA-, adriamycin-, and H3-treated mice developed CTL expressing the gamma delta+ T-cell receptors, while H310A1-infected animals did not. Only H3- and H310A1-infected mice developed alpha beta+ CTL. Treatment of BALB/c mice with 0.1 ml of CFA 5 days prior to H310A1 infection dramatically increased myocarditis. Selective depletion of gamma delta+ T cells abrogated this effect. The ability of gamma delta+ T cells to augment the pathogenicity of H310A1 infection was confirmed by adoptive transfer of CFA-stimulated T cells depleted of either gamma delta- or gamma delta+ cells into H310A1-infected recipients.

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Selected References

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

  1. Allison J. P., Havran W. L. The immunobiology of T cells with invariant gamma delta antigen receptors. Annu Rev Immunol. 1991;9:679–705. doi: 10.1146/annurev.iy.09.040191.003335. [DOI] [PubMed] [Google Scholar]
  2. Carbone A., Harbeck R., Dallas A., Nemazee D., Finkel T., O'Brien R., Kubo R., Born W. Alpha beta T-lymphocyte depleted mice, a model for gamma delta T-lymphocyte functional studies. Immunol Rev. 1991 Apr;120:35–50. doi: 10.1111/j.1600-065x.1991.tb00586.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Carding S. R., Allan W., Kyes S., Hayday A., Bottomly K., Doherty P. C. Late dominance of the inflammatory process in murine influenza by gamma/delta + T cells. J Exp Med. 1990 Oct 1;172(4):1225–1231. doi: 10.1084/jem.172.4.1225. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chantry D., Turner M., Brennan F., Kingsbury A., Feldmann M. Granulocyte-macrophage colony stimulating factor induces both HLA-DR expression and cytokine production by human monocytes. Cytokine. 1990 Jan;2(1):60–67. doi: 10.1016/1043-4666(90)90044-t. [DOI] [PubMed] [Google Scholar]
  5. Cunningham M. W., Antone S. M., Gulizia J. M., McManus B. M., Fischetti V. A., Gauntt C. J. Cytotoxic and viral neutralizing antibodies crossreact with streptococcal M protein, enteroviruses, and human cardiac myosin. Proc Natl Acad Sci U S A. 1992 Feb 15;89(4):1320–1324. doi: 10.1073/pnas.89.4.1320. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Edington H., Mayer D., Au F. C., Elfenbein I. B., Bove A. A., Smalley R. V. Effects of intravenous versus intraatrial administration of doxorubicin on the function and structure of the heart. J Surg Oncol. 1984 Sep;27(1):12–17. doi: 10.1002/jso.2930270104. [DOI] [PubMed] [Google Scholar]
  7. Gaspari A. A., Jenkins M. K., Katz S. I. Class II MHC-bearing keratinocytes induce antigen-specific unresponsiveness in hapten-specific Th1 clones. J Immunol. 1988 Oct 1;141(7):2216–2220. [PubMed] [Google Scholar]
  8. Gauntt C. J., Arizpe H. M., Higdon A. L., Rozek M. M., Crawley R., Cunningham M. W. Anti-Coxsackievirus B3 neutralizing antibodies with pathological potential. Eur Heart J. 1991 Aug;12 (Suppl 500):124–129. doi: 10.1093/eurheartj/12.suppl_d.124. [DOI] [PubMed] [Google Scholar]
  9. Germain R. N. Immunology. The ins and outs of antigen processing and presentation. Nature. 1986 Aug 21;322(6081):687–689. doi: 10.1038/322687a0. [DOI] [PubMed] [Google Scholar]
  10. Holoshitz J., Koning F., Coligan J. E., De Bruyn J., Strober S. Isolation of CD4- CD8- mycobacteria-reactive T lymphocyte clones from rheumatoid arthritis synovial fluid. Nature. 1989 May 18;339(6221):226–229. doi: 10.1038/339226a0. [DOI] [PubMed] [Google Scholar]
  11. Hufnagel G., Maisch B. Expression of MHC class I and II antigens and the Il-2 receptor in rejection, myocarditis and dilated cardiomyopathy. Eur Heart J. 1991 Aug;12 (Suppl 500):137–140. doi: 10.1093/eurheartj/12.suppl_d.137. [DOI] [PubMed] [Google Scholar]
  12. Janeway C. A., Jr, Jones B., Hayday A. Specificity and function of T cells bearing gamma delta receptors. Immunol Today. 1988 Mar;9(3):73–76. doi: 10.1016/0167-5699(88)91267-4. [DOI] [PubMed] [Google Scholar]
  13. LaThangue N. B., Shriver K., Dawson C., Chan W. L. Herpes simplex virus infection causes the accumulation of a heat-shock protein. EMBO J. 1984 Feb;3(2):267–277. doi: 10.1002/j.1460-2075.1984.tb01796.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Leslie K., Blay R., Haisch C., Lodge A., Weller A., Huber S. Clinical and experimental aspects of viral myocarditis. Clin Microbiol Rev. 1989 Apr;2(2):191–203. doi: 10.1128/cmr.2.2.191. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Long E. O., Jacobson S. Pathways of viral antigen processing and presentation to CTL: defined by the mode of virus entry? Immunol Today. 1989 Feb;10(2):45–48. doi: 10.1016/0167-5699(89)90303-4. [DOI] [PubMed] [Google Scholar]
  16. Loudon R. P., Moraska A. F., Huber S. A., Schwimmbeck P., Schultheiss P. An attenuated variant of Coxsackievirus B3 preferentially induces immunoregulatory T cells in vivo. J Virol. 1991 Nov;65(11):5813–5819. doi: 10.1128/jvi.65.11.5813-5819.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Matis L. A., Cron R., Bluestone J. A. Major histocompatibility complex-linked specificity of gamma delta receptor-bearing T lymphocytes. Nature. 1987 Nov 19;330(6145):262–264. doi: 10.1038/330262a0. [DOI] [PubMed] [Google Scholar]
  18. Miyawaki T., Kasahara Y., Taga K., Yachie A., Taniguchi N. Differential expression of CD45RO (UCHL1) and its functional relevance in two subpopulations of circulating TCR-gamma/delta+ lymphocytes. J Exp Med. 1990 May 1;171(5):1833–1838. doi: 10.1084/jem.171.5.1833. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Mueller D. L., Jenkins M. K., Schwartz R. H. Clonal expansion versus functional clonal inactivation: a costimulatory signalling pathway determines the outcome of T cell antigen receptor occupancy. Annu Rev Immunol. 1989;7:445–480. doi: 10.1146/annurev.iy.07.040189.002305. [DOI] [PubMed] [Google Scholar]
  20. Neu N., Rose N. R., Beisel K. W., Herskowitz A., Gurri-Glass G., Craig S. W. Cardiac myosin induces myocarditis in genetically predisposed mice. J Immunol. 1987 Dec 1;139(11):3630–3636. [PubMed] [Google Scholar]
  21. O'Brien R. L., Happ M. P., Dallas A., Palmer E., Kubo R., Born W. K. Stimulation of a major subset of lymphocytes expressing T cell receptor gamma delta by an antigen derived from Mycobacterium tuberculosis. Cell. 1989 May 19;57(4):667–674. doi: 10.1016/0092-8674(89)90135-9. [DOI] [PubMed] [Google Scholar]
  22. Oldstone M. B. Molecular mimicry and autoimmune disease. Cell. 1987 Sep 11;50(6):819–820. doi: 10.1016/0092-8674(87)90507-1. [DOI] [PubMed] [Google Scholar]
  23. Ozols R. F., Locker G. Y., Doroshow J. H., Grotzinger K. R., Myers C. E., Fisher R. I., Young R. C. Chemotherapy for murine ovarian cancer: a rationale for ip therapy with adriamycin. Cancer Treat Rep. 1979 Feb;63(2):269–273. [PubMed] [Google Scholar]
  24. Paque R. E., Miller R. Monoclonal anti-idiotypic antibodies regulate the expression of virus-induced murine myocarditis. Infect Immun. 1989 Sep;57(9):2864–2871. doi: 10.1128/iai.57.9.2864-2871.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Ptak W., Rozycka D., Askenase P. W., Gershon R. K. Role of antigen-presenting cells in the development and persistence of contact hypersensitivity. J Exp Med. 1980 Feb 1;151(2):362–375. doi: 10.1084/jem.151.2.362. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Rajasekar R., Sim G. K., Augustin A. Self heat shock and gamma delta T-cell reactivity. Proc Natl Acad Sci U S A. 1990 Mar;87(5):1767–1771. doi: 10.1073/pnas.87.5.1767. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Reardon C., Lefrancois L., Farr A., Kubo R., O'Brien R., Born W. Expression of gamma/delta T cell receptors on lymphocytes from the lactating mammary gland. J Exp Med. 1990 Oct 1;172(4):1263–1266. doi: 10.1084/jem.172.4.1263. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Saegusa J., Prabhakar B. S., Essani K., McClintock P. R., Fukuda Y., Ferrans V. J., Notkins A. L. Monoclonal antibody to coxsackievirus B4 reacts with myocardium. J Infect Dis. 1986 Feb;153(2):372–373. doi: 10.1093/infdis/153.2.372. [DOI] [PubMed] [Google Scholar]
  29. Schultheiss H. P., Kühl U., Janda I., Melzner B., Ulrich G., Morad M. Antibody-mediated enhancement of calcium permeability in cardiac myocytes. J Exp Med. 1988 Dec 1;168(6):2105–2119. doi: 10.1084/jem.168.6.2105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Singal P. K., Deally C. M., Weinberg L. E. Subcellular effects of adriamycin in the heart: a concise review. J Mol Cell Cardiol. 1987 Aug;19(8):817–828. doi: 10.1016/s0022-2828(87)80392-9. [DOI] [PubMed] [Google Scholar]
  31. Srinivasappa J., Saegusa J., Prabhakar B. S., Gentry M. K., Buchmeier M. J., Wiktor T. J., Koprowski H., Oldstone M. B., Notkins A. L. Molecular mimicry: frequency of reactivity of monoclonal antiviral antibodies with normal tissues. J Virol. 1986 Jan;57(1):397–401. doi: 10.1128/jvi.57.1.397-401.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Van Houten N., Bouchard P. E., Moraska A., Huber S. A. Selection of an attenuated Coxsackievirus B3 variant, using a monoclonal antibody reactive to myocyte antigen. J Virol. 1991 Mar;65(3):1286–1290. doi: 10.1128/jvi.65.3.1286-1290.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Weigle W. O., Scheuer W. V., Hobbs M. V., Morgan E. L., Parks D. E. Modulation of the induction and circumvention of immunological tolerance to human gamma-globulin by interleukin 1. J Immunol. 1987 Apr 1;138(7):2069–2074. [PubMed] [Google Scholar]
  34. Woodruff J. F., Woodruff J. J. Involvement of T lymphocytes in the pathogenesis of coxsackie virus B3 heart disease. J Immunol. 1974 Dec;113(6):1726–1734. [PubMed] [Google Scholar]
  35. Young R. A. Stress proteins and immunology. Annu Rev Immunol. 1990;8:401–420. doi: 10.1146/annurev.iy.08.040190.002153. [DOI] [PubMed] [Google Scholar]
  36. Yuuki H., Yoshikai Y., Kishihara K., Iwasaki A., Matsuzaki G., Takimoto H., Nomoto K. Clonal anergy in self-reactive alpha/beta T cells is abrogated by heat-shock protein-reactive gamma/delta T cells in aged athymic nude mice. Eur J Immunol. 1990 Jul;20(7):1475–1482. doi: 10.1002/eji.1830200711. [DOI] [PubMed] [Google Scholar]

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