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. 1984 Jan 1;159(1):77–88. doi: 10.1084/jem.159.1.77

Immunocytochemical identification and quantitation of the mononuclear cells in the cerebrospinal fluid, meninges, and brain during acute viral meningoencephalitis

PMCID: PMC2187197  PMID: 6363596

Abstract

The mononuclear cells of the central nervous system (CNS) inflammatory response were characterized in cerebrospinal fluid (CSF), meningeal exudate, and brain parenchyma of mice 3-14 d after infection with Sindbis virus. The inflammatory infiltrate in CSF peaked and resolved before that of the parenchyma or meningeal exudate. Immunoperoxidase staining with monoclonal antibodies identified CSF inflammatory cells to be almost exclusively T cells, while inflammatory cells in the brain parenchymal perivascular cuffs and the meninges were a mixture of T cells, B cells, and macrophages. The percentage of B cells and macrophages increased at the later time points. Approximately 20% of CSF and 50% of the cells present early in the perivascular cuffs were not identified, suggesting that another subset of inflammatory cells may be present. We concluded that significant differences exist in the time course and cellular composition of the inflammatory responses in different compartments of the CNS during an acute viral infection.

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Selected References

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  1. Austyn J. M., Gordon S. F4/80, a monoclonal antibody directed specifically against the mouse macrophage. Eur J Immunol. 1981 Oct;11(10):805–815. doi: 10.1002/eji.1830111013. [DOI] [PubMed] [Google Scholar]
  2. Berger M. L. Immunologic requirements for the adoptive transfer of ectromelia virus meningitis. J Neuropathol Exp Neurol. 1982 Jan;41(1):18–33. doi: 10.1097/00005072-198201000-00003. [DOI] [PubMed] [Google Scholar]
  3. Berger M. L. The role of the major histocompatibility complex in the adoptive transfer of ectromelia virus meningitis. J Neuropathol Exp Neurol. 1982 Jan;41(1):34–44. doi: 10.1097/00005072-198201000-00004. [DOI] [PubMed] [Google Scholar]
  4. 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]
  5. Blinzinger K., Herrlinger H., Luh S., Anzil A. P. Ultrastructural cytochemical demonstration of peroxidase-positive monocyte granules: an additional method for studying the origin of mononuclear cells in encephalitic lesions. Acta Neuropathol. 1978 Aug 7;43(1-2):55–61. doi: 10.1007/BF00684998. [DOI] [PubMed] [Google Scholar]
  6. Cantor H., Boyse E. A. Functional subclasses of T-lymphocytes bearing different Ly antigens. I. The generation of functionally distinct T-cell subclasses is a differentiative process independent of antigen. J Exp Med. 1975 Jun 1;141(6):1376–1389. doi: 10.1084/jem.141.6.1376. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Coffman R. L., Weissman I. L. A monoclonal antibody that recognizes B cells and B cell precursors in mice. J Exp Med. 1981 Feb 1;153(2):269–279. doi: 10.1084/jem.153.2.269. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Doherty P. C., Dunlop M. B., Parish C. R., Zinkernagel R. M. Inflammatory process in murine lymphocytic choriomeningitis is maximal in H-2K or H-2D compatible interactions. J Immunol. 1976 Jul;117(1):187–190. [PubMed] [Google Scholar]
  9. Doherty P. C., Korngold R. Characteristics of poxvirus-induced meningitis: virus-specific and non-specific cytotoxic effectors in the inflammatory exudate. Scand J Immunol. 1983 Jul;18(1):1–7. doi: 10.1111/j.1365-3083.1983.tb00828.x. [DOI] [PubMed] [Google Scholar]
  10. Doherty P. C. Quantitative studies of the inflammatory process in fatal viral meningoencephalitis. Am J Pathol. 1973 Dec;73(3):607–622. [PMC free article] [PubMed] [Google Scholar]
  11. 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]
  12. Esiri M. M. Poliomyelitis: immunoglobulin-containing cells in the central nervous system in acute and convalescent phases of the human disease. Clin Exp Immunol. 1980 Apr;40(1):42–48. [PMC free article] [PubMed] [Google Scholar]
  13. Gangji D., Collard-Ronge E., Balleriaux-Waha D., Hildebrand J., Stryckmans P. A. Letter: T lymphocytes in cerebrospinal fluid. N Engl J Med. 1976 Apr 15;294(16):902–902. doi: 10.1056/nejm197604152941614. [DOI] [PubMed] [Google Scholar]
  14. Griffin D. E. Immunoglobulins in the cerebrospinal fluid: changes during acute viral encephalitis in mice. J Immunol. 1981 Jan;126(1):27–31. [PubMed] [Google Scholar]
  15. Griffin D. E., Johnson R. T. Cellular immune response to viral infection: in vitro studies of lymphocytes from mice infected with Sindbis virus. Cell Immunol. 1973 Dec;9(3):426–434. doi: 10.1016/0008-8749(73)90057-9. [DOI] [PubMed] [Google Scholar]
  16. Herberman R. B., Djeu J., Kay H. D., Ortaldo J. R., Riccardi C., Bonnard G. D., Holden H. T., Fagnani R., Santoni A., Puccetti P. Natural killer cells: characteristics and regulation of activity. Immunol Rev. 1979;44:43–70. doi: 10.1111/j.1600-065x.1979.tb00267.x. [DOI] [PubMed] [Google Scholar]
  17. Hirsch R. L., Griffin D. E. The pathogenesis of Sindbis virus infection in athymic nude mice. J Immunol. 1979 Sep;123(3):1215–1218. [PubMed] [Google Scholar]
  18. Hirsch S., Gordon S. The use and limitation of monoclonal antibodies against mononuclear phagocytes. Immunobiology. 1982 Apr;161(3-4):298–307. doi: 10.1016/S0171-2985(82)80086-7. [DOI] [PubMed] [Google Scholar]
  19. Hsu S. M., Raine L., Fanger H. Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem. 1981 Apr;29(4):577–580. doi: 10.1177/29.4.6166661. [DOI] [PubMed] [Google Scholar]
  20. Hurwitz J. L., Korngold R., Doherty P. C. Specific and nonspecific T-cell recruitment in viral meningitis: possible implications for autoimmunity. Cell Immunol. 1983 Mar;76(2):397–401. doi: 10.1016/0008-8749(83)90383-0. [DOI] [PubMed] [Google Scholar]
  21. Johnson R. T., McFarland H. F., Levy S. E. Age-dependent resistance to viral encephalitis: studies of infections due to Sindbis virus in mice. J Infect Dis. 1972 Mar;125(3):257–262. doi: 10.1093/infdis/125.3.257. [DOI] [PubMed] [Google Scholar]
  22. Kitamura T. Hematogenous cells in experimental Japanese encephalitis. Acta Neuropathol. 1975 Oct 1;32(4):341–346. doi: 10.1007/BF00696796. [DOI] [PubMed] [Google Scholar]
  23. Ledbetter J. A., Rouse R. V., Micklem H. S., Herzenberg L. A. T cell subsets defined by expression of Lyt-1,2,3 and Thy-1 antigens. Two-parameter immunofluorescence and cytotoxicity analysis with monoclonal antibodies modifies current views. J Exp Med. 1980 Aug 1;152(2):280–295. doi: 10.1084/jem.152.2.280. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Leung K. N., Ada G. L. Induction of natural killer cells during murine influenza virus infection. Immunobiology. 1981;160(3-4):352–366. doi: 10.1016/s0171-2985(81)80061-7. [DOI] [PubMed] [Google Scholar]
  25. Manconi P. E., Zaccheo D., Bugiani O., Fadda M. F., Grifoni V., Mantovani G., Del Giacco G. S., Tognella S. Letter: T and B lymphocytes in normal cerebrospinal fluid. N Engl J Med. 1976 Jan 1;294(1):49–49. [PubMed] [Google Scholar]
  26. McFarland H. F., Griffin D. E., Johnson R. T. Specificity of the inflammatory response in viral encephalitis. I. Adoptive immunization of immunosuppressed mice infected with Sindbis virus. J Exp Med. 1972 Aug 1;136(2):216–226. doi: 10.1084/jem.136.2.216. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. McFarland H. F. In vitro studies of cell-mediated immunity in an acute viral infection. J Immunol. 1974 Jul;113(1):173–180. [PubMed] [Google Scholar]
  28. Mokhtarian F., Griffin D. E., Hirsch R. L. Production of mononuclear cell chemotactic factors during Sindbis virus infection of mice. Infect Immun. 1982 Mar;35(3):965–973. doi: 10.1128/iai.35.3.965-973.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Morishima T., Hayashi K. Meningeal exudate cells in vaccinia meningitis of mice: role of local T cells. Infect Immun. 1978 Jun;20(3):752–759. doi: 10.1128/iai.20.3.752-759.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Moser R. P., Robinson J. A., Prostko E. R. Lymphocyte subpopulations in human cerebrospinal fluid. Neurology. 1976 Aug;26(8):726–728. doi: 10.1212/wnl.26.8.726. [DOI] [PubMed] [Google Scholar]
  31. Naess A. Demonstration of T lymphocytes in cerebrospinal fluid. Scand J Immunol. 1976;5(1-2):165–168. doi: 10.1111/j.1365-3083.1976.tb03004.x. [DOI] [PubMed] [Google Scholar]
  32. Oehmichen M., Grüninger H., Wiethölter H., Gencic M. Lymphatic efflux of intracerebrally injected cells. Acta Neuropathol. 1979 Jan 12;45(1):61–65. doi: 10.1007/BF00691806. [DOI] [PubMed] [Google Scholar]
  33. Owens S. L., Osebold J. W., Zee Y. C. Dynamics of B-lymphocytes in the lungs of mice exposed to aerosolized influenza virus. Infect Immun. 1981 Jul;33(1):231–238. doi: 10.1128/iai.33.1.231-238.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Sriram S., Solomon D., Rouse R. V., Steinman L. Identification of T cell subsets and B lymphocytes in mouse brain experimental allergic encephalitis lesions. J Immunol. 1982 Oct;129(4):1649–1651. [PubMed] [Google Scholar]
  35. Traugott U., Shevach E., Chiba J., Stone H. J., Raine C. S. Autoimmune encephalomyelitis: simultaneous identification of T and B cells in the target organ. Science. 1981 Dec 11;214(4526):1251–1253. doi: 10.1126/science.7029715. [DOI] [PubMed] [Google Scholar]
  36. Walker D. H., Murphy F. A., Whitfield S. G., Bauer S. P. Lymphocytic choriomeningitis: ultrastructural pathology. Exp Mol Pathol. 1975 Oct;23(2):245–265. doi: 10.1016/0014-4800(75)90022-2. [DOI] [PubMed] [Google Scholar]
  37. Williams A. F., Gagnon J. Neuronal cell Thy-1 glycoprotein: homology with immunoglobulin. Science. 1982 May 14;216(4547):696–703. doi: 10.1126/science.6177036. [DOI] [PubMed] [Google Scholar]
  38. Zinkernagel R. M., Doherty P. C. Cytotoxic thymus-derived lymphocytes in cerebrospinal fluid of mice with lymphocytic choriomeningitis. J Exp Med. 1973 Nov 1;138(5):1266–1269. doi: 10.1084/jem.138.5.1266. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Zinkernagel R. M., Doherty P. C. MHC-restricted cytotoxic T cells: studies on the biological role of polymorphic major transplantation antigens determining T-cell restriction-specificity, function, and responsiveness. Adv Immunol. 1979;27:51–177. doi: 10.1016/s0065-2776(08)60262-x. [DOI] [PubMed] [Google Scholar]
  40. Zinkernagel R. M., Welsh R. M. H-2 compatibility requirement for virus-specific T cell-mediated effector functions in vivo. I. Specificity of T cells conferring antiviral protection against lymphocytic choriomeningitis virus is associated with H-2K and H-2D. J Immunol. 1976 Nov;117(5 Pt 1):1495–1502. [PubMed] [Google Scholar]

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