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Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1994 Nov;98(2):313–318. doi: 10.1111/j.1365-2249.1994.tb06143.x

Microglial cells qualify as the stimulators of unprimed CD4+ and CD8+ T lymphocytes in the central nervous system.

E Cash 1, O Rott 1
PMCID: PMC1534421  PMID: 7955538

Abstract

The potential of central nervous system (CNS)-derived cells for initiating T cell responses is not known. Using the capacity of unprimed T cells to respond to allogeneic determinants on antigen-presenting cells (APC), we assessed the ability of microglial cells to act as stimulators of primary T cell responses in vitro. For this purpose, microglial cells were activated with lipopolysaccharide (LPS), interferon-gamma (IFN-gamma), or by phagocytosis of progenitor oligodendrocytes and subsequently tested for their ability to induce a proliferative response of naive, resting T cells. Activated microglial cells induced a significant proliferation of virgin, alloreactive CD4+ and CD8+ T lymphocytes, with a more substantial response of highly purified CD4+ than of CD8-expressing T cells. Phagocytosis activation was the most efficient stimulus to induce this APC competence on microglial cells. By contrast, IFN-gamma-pretreated, MHC-expressing astrocytes were unable to induce similar responses of alloreactive CD4+ or CD8+ T cells under the same experimental conditions. Collectively, our data suggest the role of activated microglia as the fully immunocompetent accessory cell population of the CNS.

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Selected References

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  1. Cash E., Zhang Y., Rott O. Microglia present myelin antigens to T cells after phagocytosis of oligodendrocytes. Cell Immunol. 1993 Mar;147(1):129–138. doi: 10.1006/cimm.1993.1053. [DOI] [PubMed] [Google Scholar]
  2. Chugani D. C., Kedersha N. L., Rome L. H. Vault immunofluorescence in the brain: new insights regarding the origin of microglia. J Neurosci. 1991 Jan;11(1):256–268. doi: 10.1523/JNEUROSCI.11-01-00256.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Craggs R. I., Webster H. D. Ia antigens in the normal rat nervous system and in lesions of experimental allergic encephalomyelitis. Acta Neuropathol. 1985;68(4):263–272. doi: 10.1007/BF00690828. [DOI] [PubMed] [Google Scholar]
  4. Espinosa de los Monteros A., Zhang M., De Vellis J. O2A progenitor cells transplanted into the neonatal rat brain develop into oligodendrocytes but not astrocytes. Proc Natl Acad Sci U S A. 1993 Jan 1;90(1):50–54. doi: 10.1073/pnas.90.1.50. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Giulian D. Ameboid microglia as effectors of inflammation in the central nervous system. J Neurosci Res. 1987;18(1):155-71, 132-3. doi: 10.1002/jnr.490180123. [DOI] [PubMed] [Google Scholar]
  6. Hafler D. A., Benjamin D. S., Burks J., Weiner H. L. Myelin basic protein and proteolipid protein reactivity of brain- and cerebrospinal fluid-derived T cell clones in multiple sclerosis and postinfectious encephalomyelitis. J Immunol. 1987 Jul 1;139(1):68–72. [PubMed] [Google Scholar]
  7. Hickey W. F., Kimura H. Perivascular microglial cells of the CNS are bone marrow-derived and present antigen in vivo. Science. 1988 Jan 15;239(4837):290–292. doi: 10.1126/science.3276004. [DOI] [PubMed] [Google Scholar]
  8. Hirsch M. R., Wietzerbin J., Pierres M., Goridis C. Expression of Ia antigens by cultured astrocytes treated with gamma-interferon. Neurosci Lett. 1983 Oct 31;41(1-2):199–204. doi: 10.1016/0304-3940(83)90247-1. [DOI] [PubMed] [Google Scholar]
  9. Hoffman P. M., Dhib-Jalbut S., Mikovits J. A., Robbins D. S., Wolf A. L., Bergey G. K., Lohrey N. C., Weislow O. S., Ruscetti F. W. Human T-cell leukemia virus type I infection of monocytes and microglial cells in primary human cultures. Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):11784–11788. doi: 10.1073/pnas.89.24.11784. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Lee S. C., Collins M., Vanguri P., Shin M. L. Glutamate differentially inhibits the expression of class II MHC antigens on astrocytes and microglia. J Immunol. 1992 Jun 1;148(11):3391–3397. [PubMed] [Google Scholar]
  11. Mason D. W., Simmonds S. J. The autonomy of CD8+ T cells in vitro and in vivo. Immunology. 1988 Oct;65(2):249–257. [PMC free article] [PubMed] [Google Scholar]
  12. McFarland H. F., Dhib-Jalbut S. Multiple sclerosis: possible immunological mechanisms. Clin Immunol Immunopathol. 1989 Jan;50(1 Pt 2):S96–105. doi: 10.1016/0090-1229(89)90116-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Metlay J. P., Puré E., Steinman R. M. Control of the immune response at the level of antigen-presenting cells: a comparison of the function of dendritic cells and B lymphocytes. Adv Immunol. 1989;47:45–116. doi: 10.1016/s0065-2776(08)60662-8. [DOI] [PubMed] [Google Scholar]
  14. Prineas J. W., Kwon E. E., Cho E. S., Sharer L. R. Continual breakdown and regeneration of myelin in progressive multiple sclerosis plaques. Ann N Y Acad Sci. 1984;436:11–32. doi: 10.1111/j.1749-6632.1984.tb14773.x. [DOI] [PubMed] [Google Scholar]
  15. Rott O., Tontsch U., Fleischer B. Dissociation of antigen-presenting capacity of astrocytes for peptide-antigens versus superantigens. J Immunol. 1993 Jan 1;150(1):87–95. [PubMed] [Google Scholar]
  16. Sedgwick J. D., Mössner R., Schwender S., ter Meulen V. Major histocompatibility complex-expressing nonhematopoietic astroglial cells prime only CD8+ T lymphocytes: astroglial cells as perpetuators but not initiators of CD4+ T cell responses in the central nervous system. J Exp Med. 1991 May 1;173(5):1235–1246. doi: 10.1084/jem.173.5.1235. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Sprent J., Schaefer M. Antigen-presenting cells for unprimed T cells. Immunol Today. 1989 Jan;10(1):17–23. doi: 10.1016/0167-5699(89)90060-1. [DOI] [PubMed] [Google Scholar]
  18. Tontsch U., Rott O. Cortical neurons selectively inhibit MHC class II induction in astrocytes but not in microglial cells. Int Immunol. 1993 Mar;5(3):249–254. doi: 10.1093/intimm/5.3.249. [DOI] [PubMed] [Google Scholar]
  19. Unanue E. R., Weaver C. T., Fuhlbrigge R. C., Kiely J. M., Chaplin D. D. Membrane IL-1: a key protein in antigen presentation. Ann Inst Pasteur Immunol. 1987 May-Jun;138(3):489–492. doi: 10.1016/s0769-2625(87)80064-8. [DOI] [PubMed] [Google Scholar]
  20. Vass K., Lassmann H. Intrathecal application of interferon gamma. Progressive appearance of MHC antigens within the rat nervous system. Am J Pathol. 1990 Oct;137(4):789–800. [PMC free article] [PubMed] [Google Scholar]
  21. Williams R. M., Moore M. J., Benacerraf B. Genetic control of thymus-derived cell function. IV. Mitogen responsiveness and mixed lymphocyte reactivity of thymus cells and lymph node cells from Lewis and Brown Norway rats. J Immunol. 1973 Nov;111(5):1579–1584. [PubMed] [Google Scholar]
  22. Wong G. H., Bartlett P. F., Clark-Lewis I., Battye F., Schrader J. W. Inducible expression of H-2 and Ia antigens on brain cells. Nature. 1984 Aug 23;310(5979):688–691. doi: 10.1038/310688a0. [DOI] [PubMed] [Google Scholar]

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