Abstract
Efficient immune surveillance and tissue repair within the central nervous system (CNS) are achieved through a complex and highly regulated network of interactions between resident brain cells and the immune system. Due to its unique structure and environment, the CNS exerts a strict control on the development of inflammatory and immune reactions that can be extremely injurious (Cserr and Knopf, 1992). Major features that contribute to the immune privilege of the CNS include: the presence of structural barriers such as the tight endothelial junctions of the brain vasculature restricting the passage of circulating immune cells and molecules; the lack of a lymphatic drainage; the absence of potent antigen presenting cells (APC) such as dendritic cells that capture potential antigens in the tissues and transport them to regional lymph nodes to initiate immune responses. Several other local mechanisms have been recently proposed which may actively limit immunogenic inflammation and tissue damage within the CNS. These include: the presence of mediators, such as transforming growth factor-β (TGF-β) (Cserr and Knopf, 1992) or brain lipids (Irani et al., 1997) with an immunosuppressive role; a strict downregulatory control exerted by neurons on major histocompatibility complex (MHC) antigen expression within the CNS parenchyma, thereby limiting the potential for local antigen presentation (Neumann et al., 1996); apoptotic elimination of T cells as a mean to terminate cell-mediated immune responses once they have been initiated within the CNS (Bauer et al., 1995).
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Abbas, A.K., K.M. Murphy, and A. Sher. 1996. Functional diversity of helper T lymphocytes. Nature 383: 787–793.
Agresti C., D. D’Urso, and G. Levi. 1996. Reversible inhibitory effects of interferon-gamma and tumor necrosis factor-alpha on oligodendrocyte proliferation and differentiation in vitro. Eur. J. Neurosci. 8: 1106–1116.
Aloisi F., G. Penna, J. Cerase, B. Menèndez Iglesias, and L. Adorini. 1997. IL-12 production by central nervous system microglia is inhibited by astrocytes. J. Immunol. 159: 1604–1612.
Aloisi F., G. Penna, L. Minghetti, and L. Adorini. 1998a. CD40-CD40 ligand interaction and IFN-γ are required for IL-12 but not prostaglandin E2 secretion by microglia during antigen presentation to Th1 cells. Submitted.
Aloisi F., F. Ria, G. Penna, and L. Adorini. 1998b. Microglia are more efficient than astrocytes in antigen processing and in Thl but not Th2 cell activation. J. Immunol. 160: 4671–4680.
Baggiolini, M. 1998. Chemokines and leukocyte traffic. Nature 392: 565–568.
Banchereau, J. and R.M. Steinman. 1998. Dendritic cells and the control of immunity. Nature 392: 245–252.
Bauer J., H. Wekerle, and H. Lassmann. 1995. Apoptosis in brain-specific autoimmune diseases. Curr. Opin. Immunol. 7: 839–843.
Becher B., V. Dodelet, V. Fedorowicz, and J.P. Antel. 1996. Soluble tumor necrosis factor inhibits interleukin 12 production by stimulated human adult microglial cells in vitro. J. Clin. Invest. 98: 1539–1543.
Benveniste, E.N. and D.J. Benos. 1995. TNF-α and IFN-γ-mediated signal transduction pathways: effects on glial cell gene expression and function. FASEB J. 9: 1577–1584.
Cannella, B. and C.S. Raine. 1995. The adhesion molecule and cytokine profile of multiple sclerosis lesions. Ann. Neurol. 37: 424–435.
Cash, E. and O. Rott. 1994. Microglial cells qualify as the stimulators of unprimed CD4+ and CD8+ T lymphocytes in the central nervous system. Clin. Exp. Immunol. 98: 313–318.
Chelbi-Alix, M.K., A. Brouard, C. Boissard, D. Pelaprat, W. Rostene, and M.N. Thang. 1994. Induction by vasoactive intestinal peptide of interferon α/β synthesis in glial cells but not in neurons. J. Cell. Physiol. 158: 47–54.
Cserr, H.F. and P.M. Knopf. 1992. Cervical lymphatics, the blood-brain barrier and the immunoreactivity of the brain: a new view. Immunol. Today 13: 507–512.
De Simone R., A. Giampaolo, B. Giometto, P. Gallo, G. Levi, C. Peschle, and F. Aloisi. 1995. The costimulatory molecule B7 is expressed on human microglia in culture and in multiple sclerosis acute lesions. J. Neuropathol. Exp. Neurol. 54: 175–187.
De Simone R., G. Levi, and F Aloisi. 1998. Interferon γ gene expression in rat central nervous system glial cells. Cytokine 10: 418–422.
Fontana A., W. Fierz, and H. Wekerle. 1984. Astrocytes present myelin basic protein to encephalitogenic T-cell lines. Nature 307: 273–275.
Ford, A.L., A.L. Goodsall, W.F. Hickey, and J.D. Sedgwick. 1995. Normal adult ramified microglia separated from other central nervous system macrophages by flow cytometric sorting. J. Immunol. 154: 4309–4321.
Ford, A.L., E. Foulcher, F.A. Lemckert, and J.D. Sedgwick. 1996. Microglia induce CD4 T lymphocyte final effector function and death. J. Exp. Med. 184: 1737–1745.
Frei K., C. Siepl, P. Groscurth, S. Bodmer, C. Schwerdel, and A. Fontana. 1987. Antigen presentation and tumor cytotoxicity by interferon-γ-treated microglial cells. Eur. J. Immunol. 17: 1271–1278.
Gasque P., J. Jones, S.K. Singhrao, and B.P. Morgan. 1998. Identification of an astrocyte cell population from human brain that expresses perforin, a cytotoxic protein implicated in immune defense. J. Exp. Med. 187: 451–460
Gehrmann J., Y. Matsumoto, and G.W. Kreutzberg. 1995. Microglia: intrinsic immuneffector cell of the brain. Brain Res. Rev. 20: 269–287.
Gerritse K., J.D. Laman, R.J. Noelle, A. Aruffo, J.A. Ledbetter, W.J.A. Boersma, and E. Claassen. 1996. CD40-CD40 ligand interactions in experimental allergic encephalomyelitis and multiple sclerosis. Proc. Natl. Acad. Sci. USA 93: 2499–2504.
Graeber, M.B., W.J. Streit, D. Buringer, L. Sparks, and G.W. Kreutzberg. 1992. Ultrastructural location of major histocompatibility complex (MHC) class II perivascular cells in histologically normal human brain. J. Neuropathol. Exp. Neurol. 51: 303–311.
Hayes, G.M., M.N. Woodroofe, and L.M. Cuzner. 1987. Microglia are the major cell type expressing MHC class II in human white matter. J. Neurol. Sci. 80: 25–37.
Harrison, J.K., Y. Jiang, S. Chen, Y. Xia, D. Maciejewski, R.K. McNamara, W.J. Streit, M.N. Salafranca, S. Adhikari, D.A. Thompson, P. Botti, K.B. Bacon, and L. Feng. 1998. Role for neuronally derived fractalkine in mediating interactions between neurons and CX3CRl-expressing microglia. Proc. Natl. Acad. Sci. USA 95: 10896–10901.
Hickey, W.F and H. Kimura. 1988. perivascular microglial cells of the CNS are bone-marrow derived and present antigen in vivo. Science 239: 290–292.
Irani, D.N., K.-I. Lin, and D.E. Griffin. 1997. Regulation of brain-derived T cells during acute central nervous system inflammation. J. Immunol. 158: 2318–2326.
Jenkins, M.K. and J.G. Johnson. 1993. Molecules involved in T-cell costimulation. Curr. Opin. Immunol. 5: 361–367.
Katafuchi T., K. Motomura, S. Baba, K. Ota, and T. Ori. 1997. Differential effects of tumor necrosis factor-alpha and-beta on rat ventromedial hypothalamic neurons in vitro. Am. J. Physiol. 272: R1966-R1971.
Krakowski, M.L. and T. Owens. 1997. The central nervous system environment controls effector CD4+ T cell cytokine profile in experimental allergic encephalomyelitis. Eur. J. Immunol. 27: 2840–2847.
Kreutzberg, G.W. 1996. Microglia: a sensor for pathological events in the CNS. TINS 19: 312–318.
Matsumoto, Y, H. Hanawa, M. Tsuchida, and T Abo. 1993. In situ inactivation of infiltrating T cells in the central nervous system with autoimmune encephalomyelitis. The role of astrocytes. Immunology 79: 381–388.
Meinl E., F. Aloisi, B. Ertl, F. Weber, R. De Waal Malefyt, H. Wekerle, and R. Hohlfeld. 1994. Multiple sclerosis. Immunomodulatory effects of human astrocytes on T cells. Brain 117: 1323–1330.
Minghetti, L. and G. Levi. 1998. Microglia as effector cells in brain damage and repair: focus on prostanoids and nitric oxide. Progr. Neurobiol. 54: 99–125
Morgan, B.P. and P. Gasque. 1996. Expression of complement in the brain: role in health and disease. Immunol. Today 17: 461–466.
Mosmann, T.R. and S. Sad. 1996. The expanding universe of T-cell subsets: Th1, Th2 and more. Immunol. Today 17: 138–146.
Neumann H., J. Boucraut, C. Hahnel, T. Misgeld, and H. Wekerle. 1996. Neuronal control of MHC class II inducibility in rat astrocytes and microglia. Eur. J. Neurosci. 8: 2582–2590.
Neumann H., H. Schmidt, E. Wilharm, L. Behrens, and H. Wekerle. 1997. Interferon gamma gene expression in sensory neurons: evidence for autocrine gene regulation. J. Exp. Med. 186: 2023–2031.
Neumann H., T. Misgeld, K. Matsumuro, and H. Wekerle. 1998. Neurotrophins inhibit major histocompatibility class II inducibility of microglia: Involvement of the p75 neurotrophin receptor. Proc. Natl. Acad. Sci. USA 95: 5779–5784.
Nikcevich, K.M., K.B. Gordon, L. Tan, S.D. Hurst, J.F. Kroepfl, M. Gardinier, T.A. Barrett, and S.D. Miller. 1997. IFN-γ-activated primary murine astrocytes express B7 costimulatory molecules and prime naive antigen-specific T cells. J. Immunol. 158: 614–621.
Olsson, T, S. Kelic, Bakhiet M., B. Hojeberg, PH. van der Meide, A. Ljungdahl, and K. Kristensson. 1994. Neuronal interferon-γ immunoreactivity molecule: bioactivities and purification. Eur. J. Immunol. 24: 308–314.
Raivich G., L.L. Jones, C.U. Kloss, A. Werner, H. Neumann, and G.W. Kreutzberg. 1998. Immune surveillance in the injured nervous system: T-lymphocytes invade the axotomized mouse facial motor nucleus and aggregate around sites of neuronal degeneration. J. Neurosci. 18: 5804–5816.
Ransohoff, R.M. 1997. Chemokines in neurological disease models: correlation between chemokine expression patterns and inflammatory pathology. J. Leukoc. Biol. 62: 645–652.
Sedgwick, ID., R. Müsner, S. Schwender, and V. ter Meulen. 1991. Major histocompatibility complexexpressing 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. 173: 1235–1246.
Selmaj, K.W, C.S. Raine, M. Farooq, W.T. Norton, and C.F. Brosnan. 1991. Cytokine cytotoxicity against oligodendrocytes. J. Immunol. 147: 1522–1529.
Simpson, J.E., J. Newcombe, M.L. Cuzner, and M.N. Woodroofe. 1998. Expression of monocyte chemoattractant protein-1 and other beta-chemokines by resident glia and inflammatory cells in multiple sclerosis lesions. I Neuroimmunol. 84: 238–249.
Stalder, A.K., A. Pagenstecher, N.C. Yu, C. Kincaid, C.-S. Chiang, M.V. Hobbs, F.E. Bloom, and I.L. Campbell. 1997. Lipopolysaccharide-induced IL-12 expression in the central nervous system and cultured astrocytes and microglia. I Immunol. 159: 1344–1351.
Streit, W.J and C.A. Kincaid-Colton. 1995. The brain’s immune system. Sci. Am. 273: 38–43.
Trinchieri, G 1995. Interleukin-12: A proinflammatory cytokine with immunoregulatory functions that bridge innate resistance and antigen-specific adaptive immunity. Annu. Rev. Immunol. 13: 251–276.
Vass, K. and H. Lassmann. 1990. Intrathecal application of interferon gamma: progressive appearance of of MHC antigens within the rat nervous system. Am. I Pathol. 137: 789–800.
Wekerle H., C. Linington, H. Lassmann, and R. Meyermann. 1986. Cellular immune reactivity within the CNS. TINS 9: 271–277.
Williams K., E. Ulvestad, L. Cragg, M. Blain, and IP. Antel. 1993. Induction of primary T cell responses by human glial cells. I Neurosci. Res. 36: 382–390.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1999 Springer Science+Business Media New York
About this chapter
Cite this chapter
Aloisi, F. (1999). The Role of Microglia and Astrocytes in Cns Immune Surveillance and Immunopathology. In: Matsas, R., Tsacopoulos, M. (eds) The Functional Roles of Glial Cells in Health and Disease. Advances in Experimental Medicine and Biology, vol 468. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-4685-6_10
Download citation
DOI: https://doi.org/10.1007/978-1-4615-4685-6_10
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4613-7121-2
Online ISBN: 978-1-4615-4685-6
eBook Packages: Springer Book Archive