Major histocompatibility complex class II expression by activated microglia caudal to lesions of descending tracts in the human spinal cord is not associated with a T cell response.
Schmitt, A. B.; Buss, A.; Breuer, S.et al.
2000 • In Acta Neuropathologica, 100 (5), p. 528-36
[en] Lesion-induced microglial/macrophage responses were investigated in post-mortem human spinal cord tissue of 20 patients who had died at a range of survival times after spinal trauma or brain infarction. Caudal to the spinal cord injury or brain infarction, a strong increase in the number of activated microglial cells was observed within the denervated intermediate grey matter and ventral horn of patients who died shortly after the insult (4-14 days). These cells were positive for the leucocyte common antigen (LCA) and for the major histocompatibility complex class II antigen (MHC II), with only a small proportion staining for the CD68 antigen. After longer survival times (1-4 months), MHC II-immunoreactivity (MHC II-IR) was clearly reduced in the grey matter but abundant in the white matter, specifically within the degenerating corticospinal tract, co-localising with CD68. In this fibre tract, elevated MHC II-IR and CD68-IR were still detectable 1 year after trauma or stroke. It is likely that the subsequent expression of CD68 on MHC II-positive microglia reflects the conversion to a macrophage phenotype, when cells are phagocytosing degenerating presynaptic terminals in grey matter target regions at early survival times and removing axonal and myelin debris in descending tracts at later survival times. No T or B cell invasion or involvement of co-stimulatory B7 molecules (CD80 and CD86) was observed. It is possible that the up-regulation of MHC II on microglia that lack the expression of B7 molecules may be responsible for the prevention of a T cell response, thus protecting the spinal cord from secondary tissue damage.
Disciplines :
Neurology Neurosciences & behavior
Author, co-author :
Schmitt, A. B.
Buss, A.
Breuer, S.
Brook, G. A.
Pech, K.
Martin, Didier ; Centre Hospitalier Universitaire de Liège - CHU > Neurochirurgie
Schoenen, Jean ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Neuro-anatomie
Noth, J.
Love, S.
Schroder, J. M.
Kreutzberg, G. W.
Nacimiento, W.
Language :
English
Title :
Major histocompatibility complex class II expression by activated microglia caudal to lesions of descending tracts in the human spinal cord is not associated with a T cell response.
Publication date :
2000
Journal title :
Acta Neuropathologica
ISSN :
0001-6322
eISSN :
1432-0533
Publisher :
Springer Verlag, New York, United States - New York
Avellino A.M., Hart D., Dailey A.T., MacKinnon M., Ellegala D., Kliot M. (1995) Differential macrophage responses in the peripheral and central nervous system during Wallerian degeneration of axons. Exp Neurol 136:183-198.
De Simone R., Giampaolo A., Giometto B., Gallo P., Levi G., Peschle C., Aloisi F. (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.
Dickson D.W., Lee S.C., Mattiace L.A., Yen S.H.C., Brosnan C. (1993) Microglia and cytokines in neurological disease, with special reference to AIDS and Alzheimer's disease. Glia 7:75-83.
Dusart I., Schwab M.E. (1994) Secondary cell death and the inflammatory reaction after dorsal hemisection of the rat spinal cord. Eur J Neurosci 6:712-724.
Fleischer J., Soeth E., Reiling N., Grage-Griebenow E., Flad H.D., Ernst M. (1996) Differential expression and function of CD80 (B7-1) and CD86 (B7-2) on human peripheral blood monocytes. Imunology 89:592-598.
Freedman A.S., Freeman G.J., Rhynhart K., Nadler L.M. (1991) Selective induction of B7/BB1 on interferon-gamma-stimulated monocytes: A potential mechanism for amplification of T cell activation through the CD28 pathway. Cell Immunol 137:429-437.
Freeman G.J., Freedman A.S., Segil J.M., Lee G., Whitman J.F., Nadler L.M. (1989) B7, a new number of the Ig superfamily with unique expression on activated and neoplastic B cells. J Immunol 143:2714-2722.
George R., Griffin J.W. (1994) Delayed macrophage responses and myelin clearance during Wallerian degeneration in the central nervous system: The dorsal radiculotomy model. Exp Neurol 129:225-236.
Gimmi C.D., Freeman G.J., Gribben J.G., Gray G., Nadler L.M. (1993) Human T-cell clonal anergy is induced by antigen presentation in the absence of B7 costimulation. Proc Natl Acad Sci USA 90:6586-6590.
Graeber M.B., Bise K., Mehrain P. (1994) CR3/43, a marker for actvated human microglia: Application to diagnostic neuropathology. Neuropathol Appl Neurobiol 20:406-408.
Hirschberg D.L., Yoles E., Belkin M., Schwartz M. (1994) Inflammation after axonal injury has conflicting consequences for recovery of function: Rescue of spared axons is impaired but regeneration is supported. J Immunol 50:9-16.
Kerschensteiner M., Gallmeier E., Behrens L., Leal V.V., Misgeld T., Klinkert W.E., Kolbeck R., Hoppe E., Oropeza-Wekerle R.L., Bartke I., Stadelmann C., Lassmann H., Hohlfeld R. (1999) Activated human T cells, B cells, and monocytes produce brain-derived neurotrophic factor in vitro and in inflammatory brain lesions: A neuroprotective role of inflammation?. J Exp Med 189:865-870.
Kiefer R., Gold R., Gehrmann J., Lindholm D., Wekerle H., Kreutzberg G.W. (1993) Transforming growth factor beta expression in reactive spinal cord microglia and meningeal inflammatory cells during experimental allergic neuritis. J Neurosci Res 36:391-398.
Kiefer R., Lindholm D., Kreutzberg G.W. (1993) Interleukin-6 and transforming growth factor-β1 mRNAs are induced in rat facial nucleus following motoneuron axotomy. Eur J Neurosci 5:755-781.
Klusmann I., Schwab M.E. (1997) Effects of proinflammatory cytokines in experimental spinal cord injury. Brain Res 762:173-184.
Kreutzberg G.W. (1996) Microglia: A sensor for pathology events in the CNS. Trends Neurosci 19:312-318.
Lazar D.A., Ellegala D.B., Avellino A.M., Dailey A.T., Andrus K., Kliot M. (1999) Modulation of macrophage and microglial responses to axonal injury in the peripheral and central nervous systems. Neurosurgery 45:593-600.
Levy A.I., Bolam J.P., Rye D.B., Hallanger A.E., Demuth R.M., Mesulam M.M., Wainer B.H. (1986) A light and microscopic procedure for sequential double antigen localization using diaminobenzidine and benzidine dihydrochloride. J Histochem Cytochem 34:1449-1457.
Mattiace L.A., Davies P., Dickson W.D. (1990) Detection of HLA-DR on microglia in the human brain is a function of both clinical and technical factors. Am J Pathol 136:1101-1114.
McGeer P.L., Itagaki S., McGeer E.G. (1988) Expression of the histocompatibility glycoprotein HLA-DR in neurological diseas. Acta Neuropathol 76:550-557.
McLaughlin B.J. (1972) Propriospinal and supraspinal projections to motor nuclei in the cat spinal cord. J Comp Neurol 144:457-500.
Merrill J.E., Benveniste E.N. (1996) Cytokines in inflammatory brain lesions: Helpful and harmful. Trends Neurosci 19:331-338.
Miyuki A., Yssel H., Phillips J.H., Spits H., Lanier L.L. (1993) Functional expression of B7/BB1 on activated T lymphocytes. J Exp Med 177:845-852.
Moalem G., Monsonego A., Shani Y., Cohen I.R., Schwartz M. (1999) Differential T cell response in central and periveral nerve injury: Connection with immune privilige. FASEB J 13:1207-1217.
Morioka T., Kalehua A.N., Streit W.J. (1991) The microglial reaction in the rat dorsal hippocampus following transient forebrain ischemia. J Cereb Blood Flow Metab 11:966-973.
Nacimiento W., Sappok T., Brook G.A., Toth L., Schoen S.W., Noth J., Kreutzberg G.W. (1995) Structural changes of anterior horn neurons and their synaptic input caudal to a low thoracic spinal cord hemisection in the adult rat: A light and electron microscopic study. Acta Neuropathol 90:552-564.
Nathan P.W., Smith M.C., Deacon P. (1990) The corticospinal tract in man. Course and location of fibres at different segmental levels. Brain 113:303-324.
Perry V.H., Andersson P.B., Gordon S. (1993) Macrophages and inflammation in the central nervous system. Trends Neurosci 16:268-272.
Perry V.H., Brown M.C., Andersson P.B. (1993) Macrophage responses to central and peripheral nerve injuries. Adv Neurol 59:309-314.
Rabchevsky A.G., Streit W.J. (1997) Grafting of cultured microglial cells into the lesioned spinal cord of adult rats enhances neurite outgrowth. J Neurosci Res 47:34-48.
Raivich G., Moreno-Flores M.T., Moller J.C., Kreutzberg G.W. (1994) Inhibition of posttraumatic microglial proliferation in a genetic model of macrophage colony-stimulating factor deficiency in the mouse. Eur J Neurosci 6:1615-1618.
Rapalino O., Lazarov-Spiegler O., Agranov E., Velan G.J., Yoles E., Freidakis M., Salomon A., Gepstein R., Katz A., Belkin M., Hadari M., Schwartz M. (1998) Implantation of stimulated homologues macrophages results in partial recovery of paraplegic rats. Nat Med 4:814-821.
Sasaki A., Nakazato Y. (1992) The identity of cells expressing MHC class II antigens in normal and pathological human brain. Neuropathol Appl Neurobiol 18:13-26.
Schmitt A.B., Brook G.A., Buss A., Nacimiento W., Noth J., Kreutzberg G.W. (1998) Dynamics of microglial activation in the spinal cord after cerebral infarction is revealed by expression of MHC class II antigen. Neuropathol Appl Neurobiol 24:167-176.
Schwab M.E., Bartholdy D. (1996) Degeneration and regeneration of axons in the lesioned spinal cord. Physiol Rev 76:319-370.
Schwartz R.H. (1990) A cell culture model for T lymphocyte clonal anergy. Science 248:1349-1356.
Sedgwick J.D., Schwender S., Gregersen R., Dorries R., Meulen Vter (1993) Resident macrophages (ramified microglia) of the adult brown norway rat central nervous system are constitutively major histocompatability complex class II positive. J Exp Med 177:1145-1152.
Smetanka A.M., Yee K.T., Lund R.D. (1990) Differential induction of class I and II MHC antigen expression by degenerating myelinated and unmyelinated axons. Brain Res 521:343-346.
Streit W.J., Graeber M.B., Kreutzberg G.W. (1989) Expression of Ia antigen on perivascular and microglial cells after sublethal and lethal motor neuron injury. Exp Neurol 105:115-126.
Streit W.J., Graeber M.B., Kreutzberg G.W. (1989) Peripheral nerve lesion produces increased levels of major histocompatability complex antigens in the central nervous system. J Neuroimmunol 21:117-123.
Suzumura A., Sawada M., Mokuno K., Kato K., Marunouchi T., Yamamoto H. (1993) Effects of microglia-derived cytokines on astrocyte proliferation. Restor Neurol Neurosci 5:347-352.
Tafti M., Nishino S., Liao W., Dement W.C., Mignot E. (1996) Major Histocompatibility Complex Class II molecules in the CNS: Increased microglial expression at the onset of narcolepsy in canine model. J Neurosci 16:4588-4595.
Thomas W.E. (1992) Brain macrophages: Evaluation of microglia and their functions. Brain Res Rev 17:61-74.
Thompson C.B., Lindsten T., Ledbetter J.A., Kunkel S.L., Young H.A., Emerson S.G., Leiden J.M., June C.H. (1989) CD28 activation pathway regulates the production of multiple T cell-derived lymphokines/cytokines. Proc Natl Acad Sci USA 86:1333-1337.
Vandenberghe P., Delabie J., De Boer M., De Wolf-Peeters C., Ceupens J.L. (1993) In situ expression of B7/BB1 on antigen-presenting cells and activated B cells: An immunohistochemical study. Int Immunol 5:317-321.
Vass K., Lassmann H. (1990) Intrathecal application of interferon gamma. Progressive appearance of MHC antigens within the rat nervous system. Am J Pathol 137:789-800.
Vyth-Dreese F.A., Dellemijn T.A., Majoor D., deJong D. (1995) Localization in situ of the co-stimulatory molecules B7.1, B7.2, CD40 and their ligands in normal human lymphoid tissue. Eur J Immunol 25:3023-3029.
Weinstein D.L., Walker D.G., Akiyama H., McGeer P.L. (1990) Herpes simplex virus type infection of the CNS induces major histocompatibility complex antigen expression on rat microglia. J Neurosci Res 26:55-65.
Whittemore E.R., Korotzer A.R., Etebari A., Cotman C.W. (1993) Carbachol increases intracellular free calcium in cultured rat microglia. Brain Res 621:59-64.
