Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1978 Dec;62(6):1303–1312. doi: 10.1172/JCI109251

Viral Infection-Homograft Interactions in a Murine Model

John D Hamilton 1,2,3,4, James F Fitzwilliam 1,2,3,4, K S Cheung 1,2,3,4, John Shelburne 1,2,3,4, David J Lang 1,2,3,4, D B Amos 1,2,3,4
PMCID: PMC371896  PMID: 219027

Abstract

The effects on some host defenses of murine cytomegalovirus (MCMV) and(or) EL4, a mouse ascites homograft, were studied in mice. Assays of cellular and humoral immunity in response to either or both of these perturbations were carried out by quantitation of various immune activities.

Limited studies demonstrated no effect of EL4 inoculation on the host response to MCMV by organ viral titer, duration of viral persistence, or anti MCMV complement-fixing antibody titer.

Prior infection with MCMV, however, resulted in greatly reduced numbers of splenocytes, the source in this study of immune effector cells. Residual splenocytes demonstrated less response to both phyto-hemagglutinin and lipopolysaccharide, particularly in the 2-3-wk interval after infection. Similarly, responder cells in mixed lymphocyte cultures were less reactive when derived from infected animals. Lymphocyte-mediated cytolysis of EL4 was significantly less in mice infected on the day of and 7, 14, and 21 days before the tumor homograft with a return to control levels by 28 days. 90% of the cell-mediated cytolysis could be eliminated by treatment with anti-theta serum. Serum-mediated cytolysis of EL4 was also reduced in infected animals. No suppressor cells or serum inhibitory factors could be identified in infected animals. Although alternative explanations exist, this study suggests that in infected animals there is a significant reduction in both the number and function of bone marrow-derived and thymus-derived cells directed against the alloantigens in EL4.

Full text

PDF
1303

Selected References

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

  1. AL-ASKARI S., ZWEIMAN B., LAWRENCE H. S., THOMAS L. THE EFFECT OF ENDOTOXIN ON SKIN HOMOGRAFTS IN RABBITS. J Immunol. 1964 Nov;93:742–748. [PubMed] [Google Scholar]
  2. Allison A. C. Interactions of antibodies, complement components and various cell types in immunity against viruses and pyogenic bacteria. Transplant Rev. 1974;19(0):3–55. doi: 10.1111/j.1600-065x.1974.tb00127.x. [DOI] [PubMed] [Google Scholar]
  3. Allison A. C., Virelizier J. L. Effects of viruses on immune response. Adv Nephrol Necker Hosp. 1975;5:115–133. [PubMed] [Google Scholar]
  4. BALNER H., OLD L. J., CLARKE D. A. Accelerated rejection of male skin isografts by female C57BL mice infected with Bacillus Calmette-Guerin (B.C.G.). Proc Soc Exp Biol Med. 1962 Jan;109:58–62. doi: 10.3181/00379727-109-27103. [DOI] [PubMed] [Google Scholar]
  5. Berke G., Sullivan K. A., Amos B. Rejection of ascites tumor allografts. I. Isolation, characterization, and in vitro reactivity of peritoneal lymphoid effector cells from BALB-c mice immune to EL4 leukosis. J Exp Med. 1972 Jun 1;135(6):1334–1350. doi: 10.1084/jem.135.6.1334. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Berke G., Sullivan K. A., Amos B. Rejection of ascites tumor allografts. II. A pathway for cell-mediated tumor destruction in vitro by peritoneal exudate lymphoid cells. J Exp Med. 1972 Dec 1;136(6):1594–1604. doi: 10.1084/jem.136.6.1594. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Blanden R. V. Mechanisms of recovery from a generalized viral infection: mousepox. 3. Regression infectious foci. J Exp Med. 1971 May 1;133(5):1090–1104. doi: 10.1084/jem.133.5.1090. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Blanden R. V. Mechanisms of recovery from a generalized viral infection: mousepox. I. The effects of anti-thymocyte serum. J Exp Med. 1970 Nov;132(5):1035–1054. doi: 10.1084/jem.132.5.1035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Blanden R. V. Mechanisms of recovery from a generalized viral infection: mousepox. II. Passive transfer of recovery mechanisms with immune lymphoid cells. J Exp Med. 1971 May 1;133(5):1074–1089. doi: 10.1084/jem.133.5.1074. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Blanden R. V. T cell response to viral and bacterial infection. Transplant Rev. 1974;19(0):56–88. doi: 10.1111/j.1600-065x.1974.tb00128.x. [DOI] [PubMed] [Google Scholar]
  11. Briggs J. D., Timbury M. C., Paton A. M., Bell P. R. Viral infection and renal transplant rejection. Br Med J. 1972 Dec 2;4(5839):520–522. doi: 10.1136/bmj.4.5839.520. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Canty T. G., Wunderlich J. R., Fletcher F. Qualitative and quantitative studies of cytotoxic immune cells. J Immunol. 1971 Jan;106(1):200–208. [PubMed] [Google Scholar]
  13. Chase R. M., Jr, Rapaport F. T. The bacterial induction of homograft sensitivity. I. Effects of sensitization with group A streptococci. J Exp Med. 1965 Oct 1;122(4):721–732. doi: 10.1084/jem.122.4.721. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. David D. S., Millian S. J., Whitsell J. C., Schwartz G. H., Riggio R. R., Stenzel K. H., Rubin A. L. Viral syndromes and renal homograft rejection. Ann Surg. 1972 Feb;175(2):257–259. doi: 10.1097/00000658-197202000-00017. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Dent P. B. Immunodepression by oncogenic viruses. Prog Med Virol. 1972;14:1–35. [PubMed] [Google Scholar]
  16. Doherty P. C., Zinkernagel R. M. T-cell-mediated immunopathology in viral infections. Transplant Rev. 1974;19(0):89–120. doi: 10.1111/j.1600-065x.1974.tb00129.x. [DOI] [PubMed] [Google Scholar]
  17. Eickhoff T. C. Infectious complications in renal transplant recipients. Transplant Proc. 1973 Sep;5(3):1233–1238. [PubMed] [Google Scholar]
  18. Eilber F. R., Morton D. L., Holmes E. C., Sparks F. C., Ramming K. P. Adjuvant immunotherapy with BCG in treatment of regional-lymph-node metastases from malignant melanoma. N Engl J Med. 1976 Jan 29;294(5):237–240. doi: 10.1056/NEJM197601292940501. [DOI] [PubMed] [Google Scholar]
  19. Fahey J. L., Brosman S., Ossorio R. C., O'Toole C., Zighelboim J. Immunotherapy and human tumor immunology. Ann Intern Med. 1976 Apr;84(4):454–465. doi: 10.7326/0003-4819-84-4-454. [DOI] [PubMed] [Google Scholar]
  20. Fiala M., Payne J. E., Berne T. V., Moore T. C., Henle W., Montgomerie J. Z., Chatterjee S. N., Guze L. B. Epidemiology of cytomegalovirus infection after transplantation and immunosuppression. J Infect Dis. 1975 Oct;132(4):421–433. doi: 10.1093/infdis/132.4.421. [DOI] [PubMed] [Google Scholar]
  21. Gallis H. A., Berman R. A., Cate T. R., Hamilton J. D., Gunnells J. C., Stickel D. L. Fungal infection following renal transplantation. Arch Intern Med. 1975 Sep;135(9):1163–1172. [PubMed] [Google Scholar]
  22. Gardner M. B., Officer J. E., Parker J., Estes J. D., Rongey R. W. Induction of disseminated virulent cytomegalovirus infection by immunosuppression of naturally chronically infected wild mice. Infect Immun. 1974 Oct;10(4):966–969. doi: 10.1128/iai.10.4.966-969.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Gutterman J. U., Mavligit G., Gottlieb J. A., Burgess M. A., McBride C. E., Einhorn L., Freireich E. J., Hersh E. M. Chemoimmunotherapy of disseminated malignant melanoma with dimethyl triazeno imidazole carboxamide and bacillus calmette--guérin. N Engl J Med. 1974 Sep 19;291(12):592–597. doi: 10.1056/NEJM197409192911202. [DOI] [PubMed] [Google Scholar]
  24. Hawrylko E. Immunopotentiation with BCG: dimensions of a specific antitumor response. J Natl Cancer Inst. 1975 May;54(5):1189–1197. doi: 10.1093/jnci/54.5.1189. [DOI] [PubMed] [Google Scholar]
  25. Hellman A., Fowler A. K., Steinman H. G., Buzzerd P. M. Studies of the blastogenic response of murine lymphocyte. 3. Specific viral transformation. Proc Soc Exp Biol Med. 1972 Oct;141(1):106–109. doi: 10.3181/00379727-141-36726. [DOI] [PubMed] [Google Scholar]
  26. Henney C. S., Lichtenstein L. M., Gillespie E., Rolley R. T. In vivo suppression of the immune response to alloantigen by cholera enterotoxin. J Clin Invest. 1973 Nov;52(11):2853–2857. doi: 10.1172/JCI107481. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Holmes E. C., Eilber F. R., Morton D. L. Immunotherapy of malignancy in humans. Current status. JAMA. 1975 Jun 9;232(10):1052–1055. [PubMed] [Google Scholar]
  28. Howard R. J., Miller J., Najarian J. S. Cytomegalovirus-induced immune suppression. II. Cell-mediated immunity. Clin Exp Immunol. 1974 Sep;18(1):119–126. [PMC free article] [PubMed] [Google Scholar]
  29. Howard R. J., Najarian J. S. Cytomegalovirus-induced immune suppression. I. Humoral immunity. Clin Exp Immunol. 1974 Sep;18(1):109–118. [PMC free article] [PubMed] [Google Scholar]
  30. Häyry P., Andersson L. C., Nordling S., Virolainen M. Allograft response in vitro. Transplant Rev. 1972;12:91–140. doi: 10.1111/j.1600-065x.1972.tb00054.x. [DOI] [PubMed] [Google Scholar]
  31. Kauffman C. A., Linnemann C. C., Jr, Schiff G. M., Phair J. P. Effect of viral and bacterial pneumonias on cell-mediated immunity in humans. Infect Immun. 1976 Jan;13(1):78–83. doi: 10.1128/iai.13.1.78-83.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Kleinerman E. S., Snyderman R., Daniels C. A. Depression of human monocyte chemotaxis by herpes simplex and influenza viruses. J Immunol. 1974 Nov;113(5):1562–1567. [PubMed] [Google Scholar]
  33. Lang D. J. Cytomegalovirus infections in organ transplantation and post transfusion. An hypothesis. Arch Gesamte Virusforsch. 1972;37(4):365–377. doi: 10.1007/BF01241460. [DOI] [PubMed] [Google Scholar]
  34. Liska M., Hatala M., Vrubel J. Relationship between immune response to gram-negative intestinal rods and allotransplantation reaction. Folia Biol (Praha) 1973;19(2):101–106. [PubMed] [Google Scholar]
  35. Lopez C., Simmons R. L., Mauer M., Park B., Najarian J. S., Good R. A. Role of virus infections in immunosuppressed renal transplant patients. Transplant Proc. 1973 Mar;5(1):803–808. [PubMed] [Google Scholar]
  36. Lopez C., Simmons R. L., Mauer S. M., Najarian J. S., Good R. A., Gentry S. Association of renal allograft rejection with virus infections. Am J Med. 1974 Mar;56(3):280–289. doi: 10.1016/0002-9343(74)90609-3. [DOI] [PubMed] [Google Scholar]
  37. Lopez C., Simmons R. L., Park B. H., Najarian J. S., Good R. A. Cell-mediated and humoral immune responses or renal transplant recipients with cytomegalovirus infections. Clin Exp Immunol. 1974 Apr;16(4):565–573. [PMC free article] [PubMed] [Google Scholar]
  38. Merigan T. C. Host defenses against viral disease. N Engl J Med. 1974 Feb 7;290(6):323–329. doi: 10.1056/NEJM197402072900608. [DOI] [PubMed] [Google Scholar]
  39. OLD L. J., CLARKE D. A., BENACERRAF B. Effect of Bacillus Calmette-Guerin infection on transplanted tumours in the mouse. Nature. 1959 Jul 25;184(Suppl 5):291–292. doi: 10.1038/184291a0. [DOI] [PubMed] [Google Scholar]
  40. Olding L. B., Jensen F. C., Oldstone M. B. Pathogenesis of of cytomegalovirus infection. I. Activation of virus from bone marrow-derived lymphocytes by in vitro allogenic reaction. J Exp Med. 1975 Mar 1;141(3):561–572. doi: 10.1084/jem.141.3.561. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Osborn J. E., Blazkovec A. A., Walker D. L. Immunosuppression during acute murine cytomegalovirus infection. J Immunol. 1968 Apr;100(4):835–844. [PubMed] [Google Scholar]
  42. Osborn J. E., Medearis D. N., Jr Studies of relationship between mouse cytomegalovirus and interferon. Proc Soc Exp Biol Med. 1966 Mar;121(3):819–824. doi: 10.3181/00379727-121-30897. [DOI] [PubMed] [Google Scholar]
  43. Osborn J. E., Medearis D. N., Jr Suppression of interferon and antibody and multiplication of Newcastle disease virus in cytomegalovirus infected mice. Proc Soc Exp Biol Med. 1967 Feb;124(2):347–353. doi: 10.3181/00379727-124-31740. [DOI] [PubMed] [Google Scholar]
  44. Poplack D. G., Sher N. A., Chaparas S. D., Blaese R. M. The effect of Mycobacterium bovis (Bacillus Calmette-Guérin) on macrophage random migration, chemotaxis, and pinocytosis. Cancer Res. 1976 Apr;36(4):1233–1237. [PubMed] [Google Scholar]
  45. ROWE W. P., CAPPS W. I. A new mouse virus causing necrosis of the thymus in newborn mice. J Exp Med. 1961 May 1;113:831–844. doi: 10.1084/jem.113.5.831. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Rapaport F. T., Chase R. M., Jr The bacterial induction of homograft sensitivity. II. Effects of sensitization with staphylococci and other microoorganisms. J Exp Med. 1965 Oct 1;122(4):733–744. doi: 10.1084/jem.122.4.733. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Reed C. L., Rapp F. Induction of murine p30 by superinfecting herpesviruses. J Virol. 1976 Sep;19(3):1028–1033. doi: 10.1128/jvi.19.3.1028-1033.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Rosenstreich D. L., Farrar J. J., Dougherty S. Absolute macrophage dependency of T lymphocyte activation by mitogens. J Immunol. 1976 Jan;116(1):131–139. [PubMed] [Google Scholar]
  49. Schmidt N. J., Lennette E. H., Dennis J. Hemagglutination-inhibiting antibody responses in human infections with group B coxsackieviruses. J Immunol. 1966 Feb;96(2):311–318. [PubMed] [Google Scholar]
  50. Seiger H. F., Shingleton W. W., Metzgar R. S., Buckley C. E., 3rd Immunotherapy in patients with melanoma. Ann Surg. 1973 Sep;178(3):352–359. doi: 10.1097/00000658-197309000-00015. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Selgrade M. K., Ahmed A., Sell K. W., Gershwin M. E., Steinberg A. D. Effect of murine cytomegalovirus on the in vitro responses of T and B cells to mitogens. J Immunol. 1976 May;116(5):1459–1465. [PubMed] [Google Scholar]
  52. Simmons R. L., Lopez C., Balfour H., Jr, Kalis J., Rattazzi L. C., Najarian J. S. Cytomegalovirus: Clinical virological correlations in renal transplant recipients. Ann Surg. 1974 Oct;180(4):623–634. doi: 10.1097/00000658-197410000-00028. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Simmons R. L., Tallent M. B., Kjellstrand C. M., Najarian J. S. Prevention of death after renal transplantation. I. Recognizable patterns leading to death in long-term survivors. Am J Surg. 1970 May;119(5):553–559. doi: 10.1016/0002-9610(70)90174-1. [DOI] [PubMed] [Google Scholar]
  54. St Jeor S., Weisser A. Persistence of cytomegalovirus in human lymphoblasts and peripheral leukocyte cultures. Infect Immun. 1977 Feb;15(2):402–409. doi: 10.1128/iai.15.2.402-409.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Stone H. H., Given K. S., Martin J. D., Jr Delayed rejection of skin homografts in Pseudomonas sepsis. Surg Gynecol Obstet. 1967 May;124(5):1067–1070. [PubMed] [Google Scholar]
  56. Strom T. B., Carpenter C. B., Garovoy M. R., Austen K. F., Merrill J. P., Kaliner M. The modulating influence of cyclic nucleotides upon lymphocyte-mediated cytotoxicity. J Exp Med. 1973 Aug 1;138(2):381–393. doi: 10.1084/jem.138.2.381. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Stutman O. Immunodepression and malignancy. Adv Cancer Res. 1975;22:261–422. doi: 10.1016/s0065-230x(08)60179-7. [DOI] [PubMed] [Google Scholar]
  58. Wepsic H. T., Harris S., Sander J., Alaimo J., Morris H. Enhancement of tumor growth following immunization with Bacillus Calmette-Guérin cell walls. Cancer Res. 1976 Jun;36(6):1950–1953. [PubMed] [Google Scholar]
  59. Zbar B., Bernstein I. D., Rapp H. J. Suppression of tumor growth at the site of infection with living Bacillus Calmette-Guérin. J Natl Cancer Inst. 1971 Apr;46(4):831–839. [PubMed] [Google Scholar]

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

RESOURCES