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. 2002 Nov 13;18(4):271–289. doi: 10.1016/0165-5728(88)90049-5

Differential expression and regulation of major histocompatibility complex (MHC) products in neural and glial cells of the human fetal brain

Thekla Mauerhoff 1,∗, Ricardo Pujol-Borrell 1,∗∗, Rita Mirakian 1, Gian Franco Bottazzo 1,1
PMCID: PMC7119889  PMID: 3133393

Abstract

The cells of the central nervous system (CNS) have the peculiarity of physiologically expressing very low levels of HLA molecules. In multiple sclerosis (MS), however, as in endocrine autoimmune diseases, there is a marked increase of HLA expression in the tissue (i.e. the plaques) and this is attributable not only to infiltrating cells but also to the astrocytes. To gain an insight into the regulation of HLA in the different cell types in the CNS and to compare it to that observed in the endocrine organs, we have studied the effect of the lympho/monokines interferon (IFN)-α and -γ, tumour necrosis factor (TNF)-α, and interleukin (IL)-2 and other agents on this aspect of the biology of human fetal brain cells in culture. A two-colour immunofluorescence technique which combines antibodies to diverse CNS cell markers and monoclonal antibodies (MoAbs) to the non-polymorphic region of HLA molecules was used throughout this study. In control cultures, only astrocytes expressed MHC class I, but after incubation with either IFN-γ or TNF-α oligodendrocytes acquired class I expression. Surprisingly, astrocytes became spontaneously class II positive in culture and this was greatly enhanced by IFN-γ. Other agents such as IL-2, epidermal growth factor, phorbolmyristate acetate and lectins had no effect. The expression of HLA molecules in the cells of the CNS both in basal conditions and in response to lymphokines is therefore selective and highly heterogenous, thus reflecting their intrinsic biological diversity. These findings may help to explain the features of the immunopathology of MS and also of latent viral infections of neural cells.

Keywords: Major histocompatibility complex; Fetal brain culture, human; γ-Interferon; Tumour nectrosis factor

References

  1. Bottazzo G.F., Pujol-Borrell R., Hanafusa T., Feldmann M. Role of aberrant HLA-DR expression and antigen presentation in the induction of endocrine autoimmunity. Lancet. 1983;ii:1115–1119. doi: 10.1016/s0140-6736(83)90629-3. [DOI] [PubMed] [Google Scholar]
  2. Bottazzo G.F., Todd I., Mirakian R., Belfiore A., Pujol-Borrell R. Organ-specific autoimmunity: a 1986 overview. Immunol. Rev. 1986;94:137–169. doi: 10.1111/j.1600-065X.1986.tb01168.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Collins T.T., Lapierre L.A., Fiers W., Strominger J.L., Pober J.S. Vol. 83. 1986. Recombinant human tumour necrosis factor increases mRNA levels and surface expression of HLA, A, B, C antigens in vascular endothelial cells and dermal fibroblasts in vitro; pp. 446–451. (Proc. Natl. Acad. Sci. U.S.A.). [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cowing C. Does T cell restriction to Ia limit the need for self-tolerance? Immunol. Today. 1985;6:74–76. doi: 10.1016/0167-5699(85)90018-0. [DOI] [PubMed] [Google Scholar]
  5. Dickson J.G., Flanigan T.P., Walsch F.S. Cell surface antigens of human foetal brain and dorsal root ganglion cells in tissue culture. In: Rowland L.P., editor. Human Motor Neuron Diseases. Raven Press; New York: 1982. pp. 435–451. [PubMed] [Google Scholar]
  6. Dickson J.G., Flanigan T.P., Kemshead J.T., Doherty P., Walsh P.S. Identification of cell surface antigens present exclusively on a subpopulation of astrocytes in human foetal brain cultures. J. Neuroimmunol. 1983;5:111–123. doi: 10.1016/0165-5728(83)90002-4. [DOI] [PubMed] [Google Scholar]
  7. Dickson J.G., Kesselring J., Walsh F.S., Davison A.N. Cellular distribution of O4 antigen and galactocerebroside in primary cultures of human foetal spinal cord. Acta Neuropathol. 1985;68:340–344. doi: 10.1007/BF00690838. [DOI] [PubMed] [Google Scholar]
  8. Dubois J.H., Hammond-Tooke G.D., Cuzner M.L. Expression of major histocompatibility complex antigens in neonate rat primary mixed glial cultures. J. Neuroimmunol. 1985;9:363–377. doi: 10.1016/s0165-5728(85)80036-9. [DOI] [PubMed] [Google Scholar]
  9. Eisenbarth G., Walsh F.S., Nirenberg M. Vol. 76. 1979. Monoclonal antibody to a plasma membrane antigen of neurons; pp. 4913–4917. (Proc. Natl. Acad. Sci. U.S.A.). [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Fierz W., Endler B., Beske K., Wekerle H., Fontana A. Astrocytes as antigen presenting cells. I. Induction of Ia antigen expression on astrocytes by T cells via immune interferon and its effects on antigen presentation. J. Immunol. 1985;134:3785–3793. [PubMed] [Google Scholar]
  11. Fontana A., Fierz W., Wekerle H. Astrocytes present myelin basic protein to encephalitogenic T cell lines. Nature. 1984;307:273–276. doi: 10.1038/307273a0. [DOI] [PubMed] [Google Scholar]
  12. Hanafusa T., Pujol-Borrell R., Chiovato L., Russell R.C.G., Doniach D., Bottazzo G.F. Aberrant expression of HLA-DR antigen on thyrocyte in Graves disease: relevance for autoimmunity. Lancet. 1983;ii:1111–1115. doi: 10.1016/s0140-6736(83)90628-1. [DOI] [PubMed] [Google Scholar]
  13. Hirsch M.R., Wietzerbin J., Pierres M., Goridis C. Expression of Ia antigens by cultured astrocytes with gamma interferon. Neurosci. Lett. 1983;41:199–204. doi: 10.1016/0304-3940(83)90247-1. [DOI] [PubMed] [Google Scholar]
  14. Houghton A.N., Thompson T.M., Gross D., Oettgen H.F., Old L.J. Surface antigens of melanoma and melanocytes. Specificity of induction of Ia antigens by human gamma-interferon. J. Exp. Med. 1984;160:255–269. doi: 10.1084/jem.160.1.255. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kim S.V. Antigen expression by glial cells grown in culture. J. Neuroimmunol. 1985;8:255–282. doi: 10.1016/s0165-5728(85)80066-7. [DOI] [PubMed] [Google Scholar]
  16. Kim S.V., Moretto G., Shin D.H. Expression of Ia antigens on the surface of human oligodendrocytes ind astrocytes in culture. J. Neuroimmunol. 1985;10:141–149. doi: 10.1016/0165-5728(85)90004-9. [DOI] [PubMed] [Google Scholar]
  17. Lampson L.A., Fischer C.A. Vol. 81. 1984. Weak HLA and beta2-microglobulin expression of neuronal cell lines can be modulated by interferon; pp. 6476–6480. (Proc. Natl. Acad. Sci. U.S.A.). [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Lampson L.A., William F.H. Monoclonal antibody analysis of MHC expression in human brain biopsies: tissue ranging from ‘histologically normal’ to that showing different levels of glial tumour involvement. J. Immunol. 1986;136:4054–4062. [PubMed] [Google Scholar]
  19. Londei M., Lamb J.R., Bottazzo G.F., Feldmann M. Epithelial cells expressing aberrant MHC class II determinants can express antigen to cloned human T lymphocytes. Nature. 1984;312:639–641. doi: 10.1038/312639a0. [DOI] [PubMed] [Google Scholar]
  20. Londei M., Bottazzo G.F., Feldmann M. Human T cell clones from autoimmune thyroid glands: specific recognition of autologous thyroid cells. Science. 1985;228:85–87. doi: 10.1126/science.3871967. [DOI] [PubMed] [Google Scholar]
  21. Lysak R., Silberberg D.H. Cultured human oligodendrocytes and rat Schwann cells do not have immune response gene associated antigen (Ia) on their surface. Brain Res. 1983;289:285–292. doi: 10.1016/0006-8993(83)90029-x. [DOI] [PubMed] [Google Scholar]
  22. Massa P.T., Dorries R., Ter Melren V. Viral particles induces Ia antigen expression on astrocytes. Nature. 1986;320:285–292. doi: 10.1038/320543a0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Pfizenmaier K., Scheurich P., Schlutter C., Kronke M. Tumour necrosis factor enhanced HLA-A,B,C and HLA-DR gene expression in human tumor cell. J. Immunol. 1987;138:975–980. [PubMed] [Google Scholar]
  24. Pujol-Borrell R., Todd I. Inappropriate Class II expression in endocrine cells. Is it a primary event? In: Doniach D., Bottazzo G.F., editors. Vol. 1. 1987. pp. 1–27. (Balliere's Clinics Immunol. Allergy). [Google Scholar]
  25. Pujol-Borrell R., Hanafusa T., Chiovato L., Bottazzo G.F. Lectin induced expression of DR-antigens on human cultured follicular thyroid cells. Nature. 1983;303:71–73. doi: 10.1038/304071a0. [DOI] [PubMed] [Google Scholar]
  26. Pujol-Borrell R., Todd I., Doshi M., Gray D., Feldmann M., Bottazzo G.F. Differential expression and regulation of MHC products in the endocrine and exocrine cells of the human pancreas. Clin. Exp. Immunol. 1986;65:128–139. [PMC free article] [PubMed] [Google Scholar]
  27. Pujol-Borrell R., Todd I., Doshi M., Bottazzo G.F., Sutton R., Gray D., Adolf G.R., Feldmann M. HLA Class II induction in human islet cells by IFN-gamma plus TNF or LT. Nature. 1987;326:304–306. doi: 10.1038/326304a0. [DOI] [PubMed] [Google Scholar]
  28. Pulver M., Carrel S., Mach J.P., de Tribolet N. Cultured human fetal astrocyts can be induced by interferon-γ to express HLA-DR. J. Neuroimmunol. 1987;14:123–133. doi: 10.1016/0165-5728(87)90047-6. [DOI] [PubMed] [Google Scholar]
  29. Raff M.C., Fields K.L., Hakomori S.I., Mirsky R., Pruss R.M., Winter J. Cell-type specific markers for distinguishing and studying neurons and the major class of glial cells in culture. Brain Res. 1979;174:283–308. doi: 10.1016/0006-8993(79)90851-5. [DOI] [PubMed] [Google Scholar]
  30. Shen A.L.Y., Hu C., Hsia R., Tsai L., Lee L., Chang C. Cellular and antigenic properties of cultured normal and fetal brain and glioma cells. J. Neuroimmunol. 1985;8:141–151. doi: 10.1016/s0165-5728(85)80054-0. [DOI] [PubMed] [Google Scholar]
  31. Sommer I., Schachner M. Monoclonal antibodies (O1 to O4) to oligodendrocyte cell surface. An immunocytochemical study in the central nervous system. Dev. Biol. 1981;83:311–327. doi: 10.1016/0012-1606(81)90477-2. [DOI] [PubMed] [Google Scholar]
  32. Sun D., Wekerle H. Ia restricted encephalitogenic T lymphocytes mediating EAE lyse autoantigen-presenting astrocytes. Nature. 1986;320:70–72. doi: 10.1038/320070a0. [DOI] [PubMed] [Google Scholar]
  33. Suzumura A., Silberberg D.H. Expression of H2 antigen on oligodendrocytes is induced by soluble factors from concanavalin A activated T cells. Brain Res. 1985;336:171–175. doi: 10.1016/0006-8993(85)90431-7. [DOI] [PubMed] [Google Scholar]
  34. Takiguchi M., Frelinger J.A. Induction of antigen presentation ability in purified cultures of astroglia by interferon-gamma. J. Mol. Cell. Immunol. 1986;2:269–280. [PubMed] [Google Scholar]
  35. Takiguchi M., Ting J.P.Y., Buessow S.C., Boyer C., Gillespie Y., Frelinger J.A. Response of glioma cells to gamma-interferon: increase in Class II mRNA, protein and MLR stimulating ability. Eur. J. Immunol. 1985;15:809–814. doi: 10.1002/eji.1830150813. [DOI] [PubMed] [Google Scholar]
  36. Tedeschi B., Barrett J.N., Keane R.W. Astrocytes produce interferon that enhances the expression of H-2 antigens on a sub-population of brain cells. J. Cell. Biol. 1986;102:2244–2253. doi: 10.1083/jcb.102.6.2244. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Todd I., Bottazzo G.F. Laboratory investigation of autoimmune endocrine diseases. Clin. Immunol. Allergy. 1985;5:613–638. [Google Scholar]
  38. Todd I., Pujol-Borrell R., Hammond L.J., Bottazzo G.F., Feldmann M. Interferon-gamma induces HLA-DR expression by thyroid epithelium. Clin. Exp. Immunol. 1985;61:265–273. [PMC free article] [PubMed] [Google Scholar]
  39. Traugott U., Scheinberg L.C., Raine C.S. On the presence of Ia positive endothelial cells and astrocytes in multiple sclerosis lesions and its relevance to antigen presentation. J. Neuroimmunol. 1985;8:1–14. doi: 10.1016/s0165-5728(85)80043-6. [DOI] [PubMed] [Google Scholar]
  40. Wong G.H.W., Bartlett P.F., Clark-Lewis I., Battye F., Schrader J.W. Inducible expression of the H2 and Ia antigens on brain cells. Nature. 1984;310:688–691. doi: 10.1038/310688a0. [DOI] [PubMed] [Google Scholar]
  41. Wong G.H.W., Bartlett P.F., Clark-Lewis I., McKimm-Breschkin J.L., Schrader J.W. Interferon-gamma induces the expression of H-2 and Ia antigens on brain cells. J. Neuroimmunol. 1985;7:255–278. doi: 10.1016/s0165-5728(84)80026-0. [DOI] [PubMed] [Google Scholar]
  42. Zetter B.R. The endothelial cells of large and small blood vessels. Diabetes. 1981;30(Suppl. 2):24–28. doi: 10.2337/diab.30.2.s24. [DOI] [PubMed] [Google Scholar]

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