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. 2002 Nov 13;19(3):255–268. doi: 10.1016/0165-5728(88)90007-0

Delayed-type hypersensitivity response in the central nervous system during JHM virus infection requires viral specificity for protection

Stephen A Stohlman 1,2,∗, Mark A Sussman 1, Glenn K Matsushima 1, Richard A Shubin 2, Stephanie S Erlich 3
PMCID: PMC7119880  PMID: 2842378

Abstract

The JHM strain of mouse hepatitis virus (JHMV) elicits an I-A-restricted delayed-type hypersensitivity (DTH) response mediated by a Thy-1+, Lyt-1+, and CD4+ T cell. Adoptive transfer of these polyclonal CD4+ T cells from immunized mice prevents death in lethally infected recipients without significantly reducing virus titer in the central nervous system (CNS). These observations raise the possibility that the recruitment of mononuclear cells into the CNS may play a critical role in survival from a lethal CNS infection. Transient DTH response to nonviral antigens induced an accumulation of monocytes in the CNS that was maximal at 48 h post-challenge and virtually resolved by 5 days post-challenge. By contrast the induction of prolonged DTH responses resulted in the accumulation of a large number monocytes that persisted in the CNS for at least 5 days post-challenge. Neither type of DTH reaction suppressed virus replication or prevented death from concomitant lethal JHMV infection.

Keywords: Delayed-type hypersensitivity, Coronavirus, Cellular immunity

References

  1. Allison A. On the role of mononuclear phagocytes in immunity against viruses. Prog. Med. Virol. 1974;18:15–31. [PubMed] [Google Scholar]
  2. Askenase P.W., Van Loveren H. Delayed-type hypersensitivity: activation of mast cells by antigen specific T-cell factors initiates the cascade of cellular interactions. Immunol. Today. 1983;4:259–264. doi: 10.1016/0167-5699(83)90046-4. [DOI] [PubMed] [Google Scholar]
  3. Bang F.B., Warwick A. Vol. 46. 1960. Mouse macrophage as host cells for the mouse hepatitis virus and the genetic basis of their susceptibility; pp. 1065–1075. (Proc. Natl. Acad. Sci. U.S.A.). [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Buchmeier M., Lewicki H.A., Talbot P.J., Knobler R.L. Murine hepatitis virus-4 (strain JHM) induced neurological disease is modulated in vivo by monoclonal antibody. Virology. 1984;132:261–270. doi: 10.1016/0042-6822(84)90033-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Byrne J.A., Oldstone M.B.A. Biology of cloned cytotoxic T lymphocytes specific for lymphocytic choriomeningitis virus: clearance of virus in vivo. J. Virol. 1985;51:682–686. doi: 10.1128/jvi.51.3.682-686.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Erlich S.S., Fleming J.O., Stohlman S.A., Weiner L.P. Experimental neuropathology of chronic demyelination induced by a JHM virus variant (DS) Arch. Neurol. 1987;44:839–842. doi: 10.1001/archneur.1987.00520200043016. [DOI] [PubMed] [Google Scholar]
  7. Fleming J.O., Trousdale M.D., El-Zaatari F.A.K., Stohlman S.A., Weiner L.P. Pathogenicity of antigenic variants of murine coronavirus JHM selected with monoclonal antibodies. J. Virol. 1986;58:869–875. doi: 10.1128/jvi.58.3.869-875.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Geczy C.L. The role of lymphokines in delayed-type hypersensitivity reactions. Springer Semin. Immunopathol. 1984;7:321–346. doi: 10.1007/BF00201965. [DOI] [PubMed] [Google Scholar]
  9. Kyuwa S., Fujiwara K., Yamanouchi K. Genetic control of delayed-type hypersensitivity to mouse hepatitis virus in mice. Jpn. J. Exp. Med. 1984;54:217–219. [PubMed] [Google Scholar]
  10. Kyuwa S., Yamaguchi K., Hayami M., Fujiwara K. Characterization of mouse hepatitis virus-reactive T cell clones. In: Lai M.C., Stohlman S.A., editors. Coronaviruses. Plenum Press; New York: 1988. pp. 391–398. [Google Scholar]
  11. Lampert P.W., Sims J.K., Kniazeff A.J. Mechanism of demyelination in JHM virus encephalomyelitis. Acta Neuropathol. 1973;24:76–85. doi: 10.1007/BF00691421. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Lehmann-Grube F., Frenz I., Krahnert T., Schwachenwald R., Moskophidis D., Lohler J., Villeda Posada C.J. Mechanism of recovery from acute virus infection. IV. The questionable role of mononuclear phagocytes in the clearance of lymphocytic choriomeningitis virus from spleen of mice. J. Immunol. 1987;138:2282–2289. [PubMed] [Google Scholar]
  13. Liew F.Y. Regulation of delayed-type hypersensitivity to pathogens and alloantigens. Immunol. Today. 1982;3:18–23. doi: 10.1016/0167-5699(82)90119-0. [DOI] [PubMed] [Google Scholar]
  14. Mogensen S.C. Role of macrophages in natural resistance to virus infections. Microbiol. Rev. 1979;43:1–26. doi: 10.1128/mr.43.1.1-26.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Morrison L.A., Lukacher A.E., Braciale V.L., Fan D.P., Braciale T.J. Differences in antigen presentation to MHC class I- and class II-restricted influenza virus-specific cytolytic T lymphocyte clones. J. Exp. Med. 1986;163:903–921. doi: 10.1084/jem.163.4.903. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Nakanaga K., Yamanouchi K., Fujiwara K. Protective effect of monoclonal antibodies on lethal mouse hepatitis virus infection in mice. J. Virol. 1986;59:168–171. doi: 10.1128/jvi.59.1.168-171.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Nash A.A., Gell P.G.H. The delayed hypersensitivity T cell and its interactions with other T cells. Immunol. Today. 1981;2:162–165. doi: 10.1016/0167-5699(81)90095-5. [DOI] [PubMed] [Google Scholar]
  18. Sethi K.K., Omata Y., Schneweis K.E. Protection of mice from fatal herpes simplex virus type I infection by adoptive transfer of cloned virus-specific and H-2 restricted cytotoxic T lymphocytes. J. Gen. Virology. 1983;64:443–447. doi: 10.1099/0022-1317-64-2-443. [DOI] [PubMed] [Google Scholar]
  19. Stohlman S.A., Weiner L.P. Chronic central nervous system demyelination in mice after JHM virus infection. Neurology. 1981;31:38–41. doi: 10.1212/wnl.31.1.38. [DOI] [PubMed] [Google Scholar]
  20. Stohlman S.A., Brayton P.R., Fleming J.O., Weiner L.P., Lai M.M.C. Murine coronaviruses: isolation and characterization of two plaque morphology variants of the JHM neurotropic strain. J. Gen. Virol. 1982;63:265–275. doi: 10.1099/0022-1317-63-2-265. [DOI] [PubMed] [Google Scholar]
  21. Stohlman S.A., Woodward J.G., Frelinger J.A. Macrophage antiviral activity: extrinsic versus intrinsic activity. Infect. Immun. 1982;36:672–677. doi: 10.1128/iai.36.2.672-677.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Stohlman S.A., Matsushima G.K., Casteel N., Frelinger J.A. The defect in delayed-type hypersensitivity of young adult SJL mice is due to a lack of functional antigen-presenting cells. Eur. J. Immunol. 1985;15:913–916. doi: 10.1002/eji.1830150909. [DOI] [PubMed] [Google Scholar]
  23. Stohlman S.A., Matsushima G.K., Casteel N., Weiner L.P. In vivo effects of coronavirus-specific T cell clones: DTH inducer cells prevent a lethal infection but do not inhibit virus replication. J. Immunol. 1986;136:3052–3056. [PubMed] [Google Scholar]
  24. Townsend J.J. Macrophage response to herpes simplex encephalitis in immune competent and T cell-deficient mice. J. Neuroimmunol. 1985;7:195–206. doi: 10.1016/s0165-5728(84)80019-3. [DOI] [PubMed] [Google Scholar]
  25. Virelizier J.-L., Allison A.C. Correlation of persistent mouse hepatitis virus (MHV-3) infection with its effect on mouse macrophage cultures. Arch. Virol. 1976;50:279–285. doi: 10.1007/BF01317953. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Weiner L.P. Pathogenesis of demyelination induced by mouse hepatitis virus (JHM virus) Arch. Neurol. 1973;28:298–303. doi: 10.1001/archneur.1973.00490230034003. [DOI] [PubMed] [Google Scholar]
  27. Woodward J.G., Matsushima G.K., Frelinger J.A., Stohlman S.A. Production and characterization of T cell clones specific for mouse hepatitis virus, strain JHM: in vivo and in vitro analysis. J. Immunol. 1984;133:1016–1021. [PubMed] [Google Scholar]

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