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. 1993 Jun;91(6):2602–2608. doi: 10.1172/JCI116499

Accelerated rejection of murine cardiac allografts by murine cytomegalovirus-infected recipients. Lack of haplotype specificity.

J F Carlquist 1, J Shelby 1, Y L Shao 1, J H Greenwood 1, M E Hammond 1, J L Anderson 1
PMCID: PMC443324  PMID: 8390486

Abstract

Clinical studies have revealed a correlation between cytomegalovirus (CMV) infection and acute allograft rejection. Likewise, for a murine model we observed that C3H (H-2k) recipients infected with murine CMV (MCMV) rejected BALB/c (H-2d) cardiac allografts earlier than uninfected recipients (6.9 +/- 0.1 d compared with 8.1 +/- 0.6 d; P < 0.001). It has been hypothesized that MCMV epitopes crossreact with alloantigens and in this manner induce rejection. However, we also demonstrated that MCMV caused accelerated rejection in the reverse combination (C3H heart engrafted to BALB/c recipient; 7.2 +/- 0.3 and 9.4 +/- 0.4 d for infected and control animals, respectively; P < 0.001) and accelerated rejection of grafts of a third, unrelated haplotype (C57Bl/6; H-2b; 8.0 +/- 0.7 d compared with 10.1 +/- 0.6 for infected and control C3H recipients, respectively; P < 0.03). Ultraviolet (UV) inactivation of MCMV before administration to the graft recipient abrogated the ability to induce rapid rejection. Activated T lymphocytes were present in grafts from infected recipients 2 d before control recipients (P < 0.02) and, at the time of graft rejection, were almost exclusively CD8+ for both infected and control recipients. Thus, MCMV accelerated rejection appears not to result from crossreaction between MCMV epitopes and MHC products. The failure of UV-inactivated virus to accelerate rejection and the high proportion of CD8+ T cells recovered from all rejected grafts suggest that the class I pathway of antigen presentation may be important in the induction of early rejection.

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Selected References

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  1. Allan J. E., Shellam G. R., Grundy J. E. Effect of murine cytomegalovirus infection on mitogen responses in genetically resistant and susceptible mice. Infect Immun. 1982 Apr;36(1):235–242. doi: 10.1128/iai.36.1.235-242.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Buus S., Colon S., Smith C., Freed J. H., Miles C., Grey H. M. Interaction between a "processed" ovalbumin peptide and Ia molecules. Proc Natl Acad Sci U S A. 1986 Jun;83(11):3968–3971. doi: 10.1073/pnas.83.11.3968. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cantrell D. A., Smith K. A. Transient expression of interleukin 2 receptors. Consequences for T cell growth. J Exp Med. 1983 Dec 1;158(6):1895–1911. doi: 10.1084/jem.158.6.1895. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Carlquist J. F., Hammond M. E., Yowell R. L., O'Connell J. B., Anderson J. L. Correlation between class II antigen (DR) expression and interleukin-2-induced lymphocyte proliferation during acute cardiac allograft rejection. Transplantation. 1990 Oct;50(4):582–588. doi: 10.1097/00007890-199010000-00011. [DOI] [PubMed] [Google Scholar]
  5. Carlquist J. F., Shelby J., Hammond E. H., Greenwood J. H., Anderson J. L. Recovery and phenotypic identification of in vivo-activated lymphocytes from mouse cardiac allografts. Transplantation. 1990 Aug;50(2):349–351. [PubMed] [Google Scholar]
  6. Fujinami R. S., Nelson J. A., Walker L., Oldstone M. B. Sequence homology and immunologic cross-reactivity of human cytomegalovirus with HLA-DR beta chain: a means for graft rejection and immunosuppression. J Virol. 1988 Jan;62(1):100–105. doi: 10.1128/jvi.62.1.100-105.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Grattan M. T., Moreno-Cabral C. E., Starnes V. A., Oyer P. E., Stinson E. B., Shumway N. E. Cytomegalovirus infection is associated with cardiac allograft rejection and atherosclerosis. JAMA. 1989 Jun 23;261(24):3561–3566. [PubMed] [Google Scholar]
  8. Grundy J. E., Shearer G. M. The effect of cytomegalovirus infection on the host response to foreign and hapten-modified self histocompatibility antigens. Transplantation. 1984 May;37(5):484–490. doi: 10.1097/00007890-198405000-00013. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. Kelsey D. K., Olsen G. A., Overall J. C., Jr, Glasgow L. A. Alteration of host defense mechanisms by murine cytomegalovirus infection. Infect Immun. 1977 Dec;18(3):754–760. doi: 10.1128/iai.18.3.754-760.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. 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]
  12. Moore M. W., Carbone F. R., Bevan M. J. Introduction of soluble protein into the class I pathway of antigen processing and presentation. Cell. 1988 Sep 9;54(6):777–785. doi: 10.1016/s0092-8674(88)91043-4. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. Parronchi P., De Carli M., Manetti R., Simonelli C., Sampognaro S., Piccinni M. P., Macchia D., Maggi E., Del Prete G., Romagnani S. IL-4 and IFN (alpha and gamma) exert opposite regulatory effects on the development of cytolytic potential by Th1 or Th2 human T cell clones. J Immunol. 1992 Nov 1;149(9):2977–2983. [PubMed] [Google Scholar]
  15. Rand K. H., Pollard R. B., Merigan T. C. Increased pulmonary superinfections in cardiac-transplant patients undergoing primary cytomegalovirus infection. N Engl J Med. 1978 Apr 27;298(17):951–953. doi: 10.1056/NEJM197804272981705. [DOI] [PubMed] [Google Scholar]
  16. Rubin R. H., Tolkoff-Rubin N. E., Oliver D., Rota T. R., Hamilton J., Betts R. F., Pass R. F., Hillis W., Szmuness W., Farrell M. L. Multicenter seroepidemiologic study of the impact of cytomegalovirus infection on renal transplantation. Transplantation. 1985 Sep;40(3):243–249. doi: 10.1097/00007890-198509000-00004. [DOI] [PubMed] [Google Scholar]
  17. Shao Y. L., Shelby J., Hisatake G., Kern E. R., Nelson E. W., Gay W. A. Accelerated cardiac allograft rejection in murine cytomegalovirus-infected C3H recipients. Transplant Proc. 1991 Feb;23(1 Pt 1):129–130. [PubMed] [Google Scholar]
  18. Townsend A., Bodmer H. Antigen recognition by class I-restricted T lymphocytes. Annu Rev Immunol. 1989;7:601–624. doi: 10.1146/annurev.iy.07.040189.003125. [DOI] [PubMed] [Google Scholar]
  19. van den Berg A. P., van der Bij W., van Son W. J., Anema J., van der Giessen M., Schirm J., Tegzess A. M., The T. H. Cytomegalovirus antigenemia as a useful marker of symptomatic cytomegalovirus infection after renal transplantation--a report of 130 consecutive patients. Transplantation. 1989 Dec;48(6):991–995. doi: 10.1097/00007890-198912000-00019. [DOI] [PubMed] [Google Scholar]
  20. van der Bruggen P., Traversari C., Chomez P., Lurquin C., De Plaen E., Van den Eynde B., Knuth A., Boon T. A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. Science. 1991 Dec 13;254(5038):1643–1647. doi: 10.1126/science.1840703. [DOI] [PubMed] [Google Scholar]

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