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. 1995;131(3):159–166. doi: 10.1007/BF01102895

L3T4(CD4)-, Lyt-2(CD8)- and Mac-1(CD11b)-phenotypic leukocytes in murine cryptococcal meningoencephalitis

Peter Dobrick 1,, Klaus Miksits 1, Helmut Hahn 1
PMCID: PMC7089192  PMID: 8587582

Abstract

An immunohistological study of L3T4(CD4)+ and LYT-2(CD8)+ lymphocytes, Mac-1(CD11b)+ monocytes and granulocytes in experimental murine cryptococcal meningoencephalitis was conducted. To assess the concomitant inflammatory reaction in an extracerebral site, livers were examined in parallel. Mice were infected i.v. withCryptococcus neoformans, group A/D, and organs were examined immunohistologically for CD4-, CD8- and monocyteand granulocyte-specific CD11b-phenotypic leukocytes over a period of 60 days. Intracerebrally, agglomerations of cryptococci formed pseudocysts that were surrounded by CD4+ and CD8+ lymphocytes at the end of the second week post-infection, followed by the invasion of monocytes and granulocytes into the lesions. After the fourth week post-infection, most of the invaded lesions were transformed into glious scars. Meningitis was usually marked and showed a homogenous distribution of CD4-, CD8- and CD11b-phenotypic cells, with a predominance of monocytes and CD4+ lymphocytes. Inflammatory infiltrates in the liver were found already 4 days post-infection. CD4+ lymphocytes and monocytes were distributed homogenously in the infiltrates, with a lower number of CD8+ lymphocytes being located rather in the periphery of the infiltrates. Comparing leukocyte kinetics in brain and liver, an important observation was the delayed immigration of immune cells at the intracerebral cryptococcal lesions as compared with the liver, and the different migration patterns of T-lymphocyte subgroups and macrophages. These results suggest that there are differential leukocyte migration patterns in the liver and brain following disseminated cryptococcosis. The immunological aspects of the observed leukocyte kinetics are discussed.

Key words: Cryptococcus, Immunity, Immunohistology, Meningoencephalitis, Mice

References

  • 1.Arumugasamy N. Intracerebral cryptococcomas. Ann Acad Med. 1981;14:16–21. [PubMed] [Google Scholar]
  • 2.Fujita NK, Reynard M, Sapico FL, Guze LB, Edwards JE. Cryptococcal intracerebral mass lesions. Ann Int Med. 1985;94:382–8. doi: 10.7326/0003-4819-94-3-382. [DOI] [PubMed] [Google Scholar]
  • 3.Patterson TF, Andriole VT. Current concepts in cryptococcosis. Eur J Clin Microbiol Infect Dis. 1989;5:457–65. doi: 10.1007/BF01964060. [DOI] [PubMed] [Google Scholar]
  • 4.Zuger A, Louie E, Holzman RS, Simberkoff MS, Rahal JJ. Cryptococcal disease in patients with the acquired immunodeficiency syndrome. Ann Int Med. 1986;103:533–538. doi: 10.7326/0003-4819-104-2-234. [DOI] [PubMed] [Google Scholar]
  • 5.Bergmann F. Pathology of experimental cryptococcosis. Acta Pathol Scand Suppl. 1961;147:1–163. [Google Scholar]
  • 6.Mielke MEA. T-cell subsets in granulomatous inflammation and immunity toL. monocytogenes andB. abortus. Behring Inst Mitt. 1991;88:99–111. [PubMed] [Google Scholar]
  • 7.Mielke MEA, Niedobitek G, Stein H, Hahn H. Acquired resistance to L. monocytogenes is mediated by Lyt-2+ T cells independently of the influx of monocytes into granulomatous lesions. J Exp Med. 1989;170:589–94. doi: 10.1084/jem.170.2.589. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Modlin RL, Gebhard JF, Taylor CR, Rea TH. In situ characterisation of T-lymphocyte subsets in the reactional states of leprosy. Clin Exp Immunol. 1983;53:17–24. [PMC free article] [PubMed] [Google Scholar]
  • 9.Näher H, Sperling U, Takacs L, Hahn H. Dynamics of T cells of L3T4 and Lyt-2 phenotype within granulomas in murine listeriosis. Clin Exp Immunol. 1985;60:559–564. [PMC free article] [PubMed] [Google Scholar]
  • 10.Moser SA, Lyon FL, Domer JE, Williams JE. Immunization of mice by intracutaneous inoculation with viable virulentC. neoformans: Immunological and histopathological parameters. Infect Immun. 1982;35:685–696. doi: 10.1128/iai.35.2.685-696.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Hill JO, Harmsen AG. Intrapulmonary growth and dissemination of an avirulent strain ofCryptococcus neoformans in mice depleted of CD4+ and CD8+ T cells. J Exp Med. 1991;173:755–8. doi: 10.1084/jem.173.3.755. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Huffnagle GB, Yates JL, Lipscomb MF. Immunity to a pulmonaryC. neoformans infection requires both CD4+ and CD8+ T cells. J Exp Med. 1991;173:793–800. doi: 10.1084/jem.173.4.793. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Huffnagle GB, Lipscomb MF, Lovchik JA, Hoag KA, Street NE. The role of CD4+ and CD8+ T cells in the protective inflammatory response to a pulmonary cryptococcal infection. J Leukoc Biol. 1994;55:35–42. doi: 10.1002/jlb.55.1.35. [DOI] [PubMed] [Google Scholar]
  • 14.Miyazaki E, Tsuda T, Onizuka O. Immunohistochemical analysis of granulomatous lung lesions in primary pulmonary cryptococcosis. Nippon Kyobu Shikkan Gakkai Zasshi. 1991;29:444–51. [PubMed] [Google Scholar]
  • 15.Ho M, Springer TA. Mac-1 Antigen: Quantitative expression in macrophage populations and tissues, and immunofluorescent localization in spleen. J Immunol. 1982;128:2281–6. [PubMed] [Google Scholar]
  • 16.Cauley CK, Murphy JW. Response of congenitally athymic (nude) and phenotypically normal mice toC. neoformans infection. Infect Immun. 1979;23:644–51. doi: 10.1128/iai.23.3.644-651.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17.Graybill JR, Drutz DJ. Host defense in Cryptococcosis: II. Cryptococcosis in the nude mouse. Cell Immunol. 1978;40:263–74. doi: 10.1016/0008-8749(78)90334-9. [DOI] [PubMed] [Google Scholar]
  • 18.Mody CH, Tyler CL, Sitrin RG, Jackson C, Toews GB. Interferon-gamma activates rat alveolar macrophages for anticryptococcal activity. Am J Resp Cell Mol Biol. 1991;5:19–26. doi: 10.1165/ajrcmb/5.1.19. [DOI] [PubMed] [Google Scholar]
  • 19.Bulmer GS, Tacker JR. Phagocytosis ofC. neoformans by alveolar macrophages. Infect Immun. 1975;11:73–79. doi: 10.1128/iai.11.1.73-79.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20.Tacker JR, Farhi F, Bulmer GS. Intracellular fate ofC. neoformans. Infect Immun. 1972;6:162–7. doi: 10.1128/iai.6.2.162-167.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21.Mody CH, Lipscomb MF, Street NE, Toews GB. Depletion of CD4+ (L3T4+) lymphocytes in vivo impairs murine host defence toC. neoformans. J Immunol. 1990;144:1472–7. [PubMed] [Google Scholar]
  • 22.Nishimura K, Miyaji M. Histopathological studies on experimental cryptococcosis in nude mice. Mycopathologia. 1979;68:145–53. doi: 10.1007/BF00578522. [DOI] [PubMed] [Google Scholar]
  • 23.Blasi E, Barluzzi R, Mazzolla R, Bistoni F. Differential host susceptibility to intracerebral infection with Candida albicans and Cryptococcus neoformans. Infect Immun. 1993;61:3476–81. doi: 10.1128/iai.61.8.3476-3481.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24.Baba T. Electron microscopic cytochemical analysis of hepatic granuloma induced byCryptococcus neoformans. Mycopathologia. 1988;104:37–46. doi: 10.1007/BF00437922. [DOI] [PubMed] [Google Scholar]
  • 25.Blasi E, Barluzzi R, Mazzolla R, Mosci P, Bistoni F. Experimental model of intracerebral infection withCryptococcus neoformans: roles of phagocytes and opsonization. Infect Immun. 1992;60:3682–8. doi: 10.1128/iai.60.9.3682-3688.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26.Oehmichen M. Are resting and/or reactive microglia macrophages? Immunobiol. 1982;161:246–54. doi: 10.1016/S0171-2985(82)80080-6. [DOI] [PubMed] [Google Scholar]
  • 27.Roessmann U, Friede RL. Entry of labeled monocytic cells into the central nervous system. Acta Neuropathologica. 1968;10:359–62. doi: 10.1007/BF00690711. [DOI] [PubMed] [Google Scholar]
  • 28.Anderson PB, Perry VH, Gordon S. The acute inflammatory response to lipopolysaccharide in CNS parenchyma differs from that in other body sites. Neuroscience. 1992;48:169–86. doi: 10.1016/0306-4522(92)90347-5. [DOI] [PubMed] [Google Scholar]
  • 29.Engelhardt B, Conley FK, Butcher EC. Cell adhesion molecules on vessels during inflammation in the mouse central nervous system. J Neuroimmunol. 1994;51:199–208. doi: 10.1016/0165-5728(94)90082-5. [DOI] [PubMed] [Google Scholar]
  • 30.Hickey WF. Migration of hematogenous cells through the blood-brain-barrier and the initiation of CNS inflammation. Brain-Pathol. 1991;1:97–105. doi: 10.1111/j.1750-3639.1991.tb00646.x. [DOI] [PubMed] [Google Scholar]
  • 31.Lassmann H, Rossler K, Zimprich F, Vass K. Expression of adhesion molecules and histocompatibility antigens at the blood-brain-barrier. Brain-Pathol. 1991;1:115–123. doi: 10.1111/j.1750-3639.1991.tb00648.x. [DOI] [PubMed] [Google Scholar]
  • 32.Male D, Pryce G, Linke A, Rahman J. Lymphocyte migration into the CNS modelled in vitro. J Neuroimmunol. 1992;40:167–71. doi: 10.1016/0165-5728(92)90130-d. [DOI] [PubMed] [Google Scholar]
  • 33.Doherty PC, Allan JE, Lynch F, Ceredig R. Dissection of an inflammatory process induced by CD8+ T cells. Immunol Today. 1990;11:55–59. doi: 10.1016/0167-5699(90)90019-6. [DOI] [PubMed] [Google Scholar]
  • 34.Dorries R, Schwender S, Imrich H, Harms H. Population dynamics of lymphocyte subsets in the central nervous system of rats with different susceptibility to coronavirus-induced demyelinating encephalitis. Immunology. 1991;74:539–45. [PMC free article] [PubMed] [Google Scholar]
  • 35.Mody CH, Chen GH, Jackson CJ, Curtis JL, Toews GB. Depletion of murine CD8+ T cells in vivo decreases pulmonary clearance of a moderately virulent strain of Cryptococcus neoformans. J Lab Clin Med. 1993;121:765. [PubMed] [Google Scholar]
  • 36.Mody CH, Paine R, Jackson C, Chen GH, Toews GB. CD8 cells play a critical role in delayed type hypersensitivity to intact Cryptococcus neoformans. J Immunol. 1994;152:3970–9. [PubMed] [Google Scholar]
  • 37.Hill JO, Aquirre KM. CD4+ T cell-dependent acquired state of immunity that protects the brain against Cryptococcus neoformans. J Immunol. 1994;152:2344–50. [PubMed] [Google Scholar]

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