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Astrocytes and intracerebral immune responses

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Abstract

The astrocyte is the most abundant cell within the central nervous system (CNS). This cell subserves a multiplicity of important functions that contribute to the process of neural development as well as to the integrity of normal brain function. Adding to the already exhaustive list of capabilities, the astrocyte has now been demonstrated to function as an intracerebral antigen presenting cell. These findings are serving to revise our view of the brain as an immunoprivileged site and perhaps will shed some light on the pathogenetic mechanisms involved in a number of CNS disorders of immune dysregulation. In this review we provide some perspective on the regulatory mechanisms that influence astrocyte immune functions. Specifically, we address the role played by the major histocompatibility complex (MHC) antigens as well as adhesion molecules in the initiation of brain immune responses.

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References

  1. Ediden M: Transplantation Antigens. New York, Academic Press, 1972, pp 125–140

    Google Scholar 

  2. Hiesiger EM, Voorhies RM, Basler GA, Lipschultz LE, Posner JB, Shapiro WR: Opening the blood-brain and blood-tumor barriers in experimental rat brain tumors: The effect of intracarotid hyperosmolar mannitol on capillary permeability and blood flow. Ann Neurol 19:50–59, 1986

    Google Scholar 

  3. Naparstek Y, Gohen IR, Fuks Z, Vlodorsky I: Activated T lymphocytes produce a matrix-degrading heparan sulphate endoglycosidase. Nature 310:241–244, 1984

    Google Scholar 

  4. Gallatin WM, Weissman IL, Butaler EC: A cell surface molecule involved in organ-specific homing of lymphocytes. Nature 304:30–34, 1983

    Google Scholar 

  5. Hickey HF, Kimura K: Perivascular microglial cells of the CNS are bone marrow-derived and present antigen in vivo. Science 239:290–292, 1988

    Google Scholar 

  6. Lampson LA, Hichey WF: Monoclonal antibody analysis of MHC expression in human brain biopsies: Tissue ranging from histologically normal to that showing different levels of glial tumor involvement. J Immunol 136:4054–4062, 1986

    Google Scholar 

  7. Tedeschi B, Barrett JN, Keane RW: Astrocytes produce interferon that enhances the expression of H-2 antigens on a subpopulation of brain cells. J Cell Biol 102:2244–2253, 1986

    Google Scholar 

  8. Frank E, Pulver M, de Tribolet N: Expression of class II major histocompatibility antigens on reactive astrocytes and endothelial cells within the gliosis surrounding metastases and abscesses. J Neuroimmunol 12:29–66, 1986

    Google Scholar 

  9. Eng LF, Vanderhaeghen JJ, Bignami A, Gerstl B: An acidic protein isolated from fibrous astrocytes. Brain Res 28:351–354, 1971

    Google Scholar 

  10. Revel JP, Napolitano L, Fawcett DW: Identification of glycogen in electron micrographs on thin tissue sections. J Biophys Biochem Cytol 8:575–589, 1960

    Google Scholar 

  11. Dermietzel R: Junctions in the central nervous system of the cat. I. Membrane fusion in central myelin. Cell Tissue Res 149:121–135, 1974

    Google Scholar 

  12. Manthorpe M, Rudge JJ, Varon S: Astroglial cell contributions to neuronal survival and neuritic growth.In Biochem Physiol Pharm Astrocytes. Orlando, FL, Academic Press, 1986, pp 315–376

    Google Scholar 

  13. Rakic P: Guidance of neurons migrating to the fetal monkey neocortex. Brain Res 33:471–476, 1971

    Google Scholar 

  14. Rakic P: Neuron-glia relationship during granule cell migration in developing cerebellar cortex. A glogi and electron microscopic study in macacus rhesus. J Comp Neurol 141:283–312, 1971

    Google Scholar 

  15. Hertz L, Schousboe A: Role of astrocytes in compartmentation of amino acid and energy metabolism.In Biochem Physiol Pharm Astrocytes. Orlando, FL, Academic Press, 1986, pp 179–208

    Google Scholar 

  16. Lauder J: Neuronal-glial interactions.In Biochem Physiol Pharm Astrocytes. Orlando, FL, Academic Press, 1986, pp 295–314

    Google Scholar 

  17. Shain W, Madelian V, Martin DL, Kimelberg HK, Perrone M, Lepore R: Activation of β-adrenergic receptors stimulates release of an inhibitory transmitter from astrocytes. J Neurochem 46:1298–1303, 1986

    Google Scholar 

  18. ffrench-Constant C, Miller RH, Schachner M, Raff MC: Molecular specialization of astrocyte processes at nodes of Ranvier in rat optic nerve. J Cell Biol 102:844–852, 1986

    Google Scholar 

  19. Paulson OB, Newman EA: Does the release of potassium from astrocyte endfeet regulate cerebral blood flow? Science 237:896–898, 1987

    Google Scholar 

  20. Janzer RC, Raff MC: Astrocytes induce blood-brain barrier properties in endothelial cells. Nature 325:253–257, 1987

    Google Scholar 

  21. Reier PL: Gliosis following CNS injury: The anatomy of astrocytic scars and their influences on axonal elongation.In Cell Biol Pathol Astrocytes. Orlando, FL, Academic Press, 1986, pp 263–324

    Google Scholar 

  22. Murphy S, Pearce B: Functional receptors for neurotransmitters on astroglial cells. Neuroscience 22:381–394, 1987

    Google Scholar 

  23. Wong GHW, Bartlett PF, Clark-Lewis I, Battye F, Schrader JW: Inducible expression of H-2 and Ia antigens on brain cells. Nature 310:688–691, 1984

    Google Scholar 

  24. DeMaeyer E, Maeyer-Guignard J: Interferons as regulatory agents of the immune system. CRC Crit Rev Immunol 2:167–188, 1981

    Google Scholar 

  25. Fontana A, Hengartner H, de Tribolet N, Weber E: Glioblastoma cells release interleukin-1 and factors inhibiting interleukin-2 mediated effects. J Immunol 132:1837, 1984

    Google Scholar 

  26. Fontana A, Erb P, Pircher H, Zinkernagel R, Weber E, Fierz W: Astrocytes as antigen-presenting cells. II. Unlike H-2K-dependent cytotoxic cells, H-2-Ia-restricted T cells are only stimulated in the presence of interferon-γ. J Neuroimmunol 12:15–28, 1986

    Google Scholar 

  27. Rodriguez M, Pierce ML, Howie EA: Immune response gene products (Ia antigens) on glial and endothelial cells in virus induced demyelination. J Immunol 138:3438–3442, 1987

    Google Scholar 

  28. Massa PT, Dorries R, ter Meulen V: Viral particles induce Ia antigen expression on astrocytes. Nature 320:543–546, 1986

    Google Scholar 

  29. Massa PT, Schimpl A, Wecker E, ter Meulen V: Tumor necrosis factor amplifies measles virus-mediated Ia induction on astrocytes. Proc Natl Acad Sci USA 84:7242–7245, 1987

    Google Scholar 

  30. Nathan CF, Murray HW, Wiebe ME, Rubin BY: Identification of interferon-γ as the lymphokine that activates human macrophage oxidative metabolism and antimicrobial activity. J Exp Med 158:670–689, 1983

    Google Scholar 

  31. Massa PT, ter Meulen V: Analysis of Ia induction on Lewis rat astrocytes in vitro by virus particles and bacterial adjuvants. J Neuroimmunol 13:259–271, 1987

    Google Scholar 

  32. Carswell EA, Old LJ, Kassel RL, Green S, Fiure N, Williams B: An endotoxin-induced serum factor that causes necrosis of tumors. Proc Natl Acad Sci USA 72:3666–3670, 1975

    Google Scholar 

  33. Pennica D, Hayflick JJ, Bringman TJ, Palladino MA, Goeddel DV: Cloning and expression in Escherichia coli of the cDNA for murine tumor necrosis factor. Proc Natl Acad Sci USA 82:6060–6064, 1985

    Google Scholar 

  34. Wong GHW, Bartlett PE, Goeddel DV: Tumor necrosis factor α and β inhibit virus replication and synergize with interferons. Nature 323:819–822, 1986

    Google Scholar 

  35. Pujol-Burrell R, Todd I, Dushi M, Bottazo GF, Sitton R, Gray D, Adolf GR, Feldman M: HLA class II induction in human islet cells by interferon-γ plus tumor necrosis factor or lymphotoxin. Nature 326:304–306, 1987

    Google Scholar 

  36. Frohman E, Vayuvegula B, Gupta S, van den Noort S: Norepinephrine inhibits γ-interferon-induced major histocompatibility class II (Ia) antigen expression on cultured astrocytes via beta-2-adrenergic signal transduction mechanisms. Proc Natl Acad Sci USA 85:1292–1296, 1988

    Google Scholar 

  37. Frohman E, Frohman T, Vayuvegula B, Gupta S, van den Noort S: VIP inhibits MHC expression on astrocytes. J Neurol Sci (in press)

  38. Zamvil S, Nelson P, Trotter J, Mitchell D, Knobler R, Fritz R, Steinman L: T cell clones specific for myelin basic protein induce chronic relapsing paralysis and demyelination. Nature 317:355–358, 1985

    Google Scholar 

  39. Zamvil SS, Mitchell DJ, Moore AC, Kitamura K, Steinman L, Rothbard JB: T cell epitope of the autoantigen myelin basic protein that induces encephalomyelitis. Nature 324:258–260, 1986

    Google Scholar 

  40. Sakai K, Tabira T, Endoh M, Steinman L: Ia expression in chronic relapsing experimental allergic encephalomyelitis induced by long-term cultured T cell lines in mice. Lab Invest 54:345–352, 1986

    Google Scholar 

  41. Waldor MK, Sriram S, McDevitt HO, Steinman L: In vivo therapy with monolonal anti-I-A-antibody suppresses immune responses to acetylcholine receptor. Proc Natl Acad Sci USA 80:2713–2717, 1983

    Google Scholar 

  42. Steinman L, Waldor MK, Zamvil S, Lim M, Herzenberg L, Herzenberg L, McDevitt, HO, Mitchell D, Sriram S: Therapy of autoimmune diseases with antibody to immune response gene products and to T-cell surface markers. Ann NY Acad Sci 475:274–284, 1986

    Google Scholar 

  43. Waksman BH, Reingold SC: Viral etiology of multiple sclerosis: Where does the truth lie? Trends Neuro Sci 9:388–391, 1986

    Google Scholar 

  44. Weiner HL, Hauser SL: Neuroimmunology. I. Immunoregulation in neurological disease. Ann Neurol 11:437–449, 1982

    Google Scholar 

  45. Lisak RP, Barchi RL: Myasthenia gravis. Philadelphia, WB Saunders, 1982, pp 191–199

    Google Scholar 

  46. Panitch HS, Hirsch RL, Schindler J, Johnson KP: Treatment of multiple sclerosis with gamma interferon: Exacerbations associated with activation of the immune system. Neurology 37:1097–1102, 1987

    Google Scholar 

  47. Lisak RP: Imunopathogenic mechanisms, abnormal immunoregulation, and immunomodulating therapy in multiple sclerosis. Clin Asp Autoimmunol 1:14–21, 1987

    Google Scholar 

  48. Traugott U, Lebon P: Interferon-γ and Ia antigens are present on astrocytes in active chronic multiple sclerosis lesions. J Neuroimmunol 84:257–264, 1988

    Google Scholar 

  49. Campana D, Sheridan B, Tidman N, Hoffbrand AV, Janossy G: Human leucocyte function-associated antigens on lympho-hemopoietic precursor cells. Eur J Immunol 16:537–541, 1986

    Google Scholar 

  50. Dougherty GJ, Hogg N: The role of monocyte lymphocyte function-associated antigen 1 (LFA-1) in accessory cell function. Eur J Immunol 17:943–947, 1987

    Google Scholar 

  51. Rothlein R, Dustin ML, Marlin SD, Springer TA: A human intercellular adhesion molecule (ICAM-1) distinct from LFA-1. J Immunol 137:1270–1274, 1986

    Google Scholar 

  52. Dustin ML, Rothlein R, Bhan AK, Dinarello CA, Springer TA: Induction by IL 1 and interferon-γ: Tissue distribution, biochemistry, and function of a natural adherence molecule (ICAM-1). J Immunol 137:1270–1274, 1986

    Google Scholar 

  53. Simmons D, Makgoba MW, Seed B: ICAM, an adhesion ligand of LFA-1, is homologous to the neural cell adhesion molecule NCAM. Nature 331: 624–627, 1988

    Google Scholar 

  54. Frohman EM, Frohman TC, Dustin ML, Vayuregula B, Choi B, Gupta A, Van den Noort S, Gupta S: Induction of ICAM-1 expression on human fetal astrocytes by IFN-γ, TNF-γ, LT, and IL-1: Relevance to intracerebral antigen presentation (in preparation)

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Authors and Affiliations

  1. Department of Neurology, College of Medicine, University of California, 92717, Irvine, California

    Elliot M. Frohman & Stanley van den Noort

  2. Department of Medicine, College of Medicine, University of California, 92717, Irvine, California

    Sudhir Gupta

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  1. Elliot M. Frohman
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  2. Stanley van den Noort
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  3. Sudhir Gupta
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Frohman, E.M., van den Noort, S. & Gupta, S. Astrocytes and intracerebral immune responses. J Clin Immunol 9, 1–9 (1989). https://doi.org/10.1007/BF00917121

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