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Immunophenotypic analysis of infiltrating leukocytes and microglia in an experimental rat glioma

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Summary

The appearance and cellular distribution of major histocompatibility complex (MHC), as well as lymphocytic and macrophage antigens has been studied in a fully developed experimental rat forebrain glioma. Activated microglial cells and microglia-derived macrophages expressing CR3 complement receptor molecules and MHC class II (Ia) antigen were found throughout the tumor, and with increased density along the tumor's periphery. MHC class I antigen expression was entirely absent from tumor cells, and found only occasionally on microglia. The expression of leukocyte common antigen, and CD4 and CD8 antigens was conspicuous throughout the tumor, and associated with lymphocytes, perivascular cells, and microglia. Cells expressing the ED2 macrophage epitope were almost exclusively of the perivascular type and revealed a distribution dissimilar to that of cells positive for Ia antigen. The ED2 epitope was found sporadically on ramified microglial cells. The results show that despite heavy infiltration with blood mononuclear and CNS microglial cells, the tumor showed no evidence of destruction caused by inflammatory cells. Possible mechanisms of tumor immunosuppressive activity preventing the full immunological activation of microglia and blood mononuclear cells are discussed.

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References

  1. Bodmer S, Strommer K, Frei K, Siepl C, De Tribolet N, Heid I, Fontana A (1989) Immunosuppression and transforming growth factor-β in glioblastoma. J Immunol 143:3222–3229

    Google Scholar 

  2. Brideau RJ, Carter PB, McMaster WR, Mason DW, Williams AF (1980) Two subsets of rat T lymphocytes defined with monoclonal antibodies. Eur J Immunol 10:609–615

    Google Scholar 

  3. Chantry D, Turner M, Abney E, Feldmann M (1989) Modulation of cytokine production by transforming growth factor-β. J Immunol 142:4295–4300

    Google Scholar 

  4. Clark SJ, Jefferies WA, Barclay AN, Gagnon J, Williams AF (1987) Peptide and nucleotide sequence of rat CD4 (W3/25) antigen: evidence for derivation from a structure with four immunoglobulin-related domains. Proc Natl Acad Sci USA 84:1649–1653

    Google Scholar 

  5. Clark WC, Bressler J (1988) Transforming growth factor-β-like activity in tumors of the central nervous system. J Neurosurg 68:920–924

    Google Scholar 

  6. Dijkstra CD, Döpp EA, Joling P, Kraal G (1985) The heterogeneity of mononuclear phagocytes in lymphoid organs: distinct macrophage subpopulations in the rat recognized by monoclonal antibodies ED1, ED2 and ED3. Immunology 54:589–599

    Google Scholar 

  7. Esiri MM, McGee J (1986) Monoclonal antibody to macrophages (EMB 11) labels macrophages and microglial cells in human brain. J Clin Pathol 39:615–621

    Google Scholar 

  8. Frei K, Siepl C, Groscurth P, Bodmer S, Schwerdel C, Fontana A (1987) Antigen presentation and tumor cytotoxicity by interferon-γ-treated microglial cells. Eur J Immunol 17:1271–1278

    Google Scholar 

  9. Fukomoto T, McMaster WR, Williams AF (1982) Mouse monoclonal antibodies against rat major histocompatibility antigens. Two Ia antigens and expression of Ia and class I antigens in rat thymus. Eur J Immunol 12:237–243

    Google Scholar 

  10. Giulian D (1987) Ameboid microglia as effectors of inflammation in the central nervous system. J Neurosci Res 18:155–171

    Google Scholar 

  11. Graeber MB, Streit WJ (1990) Microglia: immune network in the CNS. Brain Pathol 1:2–5

    Google Scholar 

  12. Graeber MB, Streit WJ, Kreutzberg GW (1988) Axotomy of the rat facial nerve leads to increased CR3 complement receptor expression by activated microglial cells. J Neurosci Res 21:18–24

    Google Scholar 

  13. Graeber MB, Streit WJ, Kreutzberg GW (1989) Identity of ED2-positive perivascular cells in rat brain. J Neurosci Res 22:103–106

    Google Scholar 

  14. Graeber MB, Streit WJ, Kiefer R, Schoen SW, Kreutzberg GW (1990) New expression of myelomonocytic antigens by microglia and perivascular cells following lethal motor neuron injury. J Neuroimmunol 27:121–132

    Google Scholar 

  15. Hitchcock ER, Morris CS (1988) Mononuclear cell infiltration in central portions of human astrocytomas. J Neurosurg 68:432–437

    Google Scholar 

  16. Mapstone T, McMichael M, Goldthwait D (1991) Expression of platelet-derived growth factors, transforming growth factors, and the ros gene in a variety of primary human brain tumors. Neurosurgery 28:216–222

    Google Scholar 

  17. McMaster WR, Williams AF (1979) Identification of Ia glycoproteins in rat thymus and purification from rat spleen. Eur J Immunol 9:426–433

    Google Scholar 

  18. Merrill JE, Zimmermann RP (1991) Natural and induced cytotoxicity of oligodendrocytes by microglia is inhibitable by TGF-β. Glia 4:327–331

    Google Scholar 

  19. Miescher S, Whiteside TL, de Tribolet N, von Fliedner V (1988) In situ characterization, clonogenic potential, and antitumor cytolytic activity of T lymphocytes infiltrating human brain cancers. J Neurosurg 68:438–448

    Google Scholar 

  20. Morantz RA, Wood GW, Foster M, Clark M, Gollahon K (1979) Macrophages in experimental and human brain tumors. Part 1: Studies of the macrophage content of experimental rat brain tumors of varying immunogenicity. J Neurosurg 50:298–304

    Google Scholar 

  21. Morimura T, Neuchrist C, Kitz K, Budka H, Scheiner O, Kraft D, Lassmann H (1990) Monocyte subpopulations in human gliomas: expression of Fc and complement receptors and correlation with tumor proliferation. Acta Neuropathol 80:287–294

    Google Scholar 

  22. Morioka T, Streit WJ (1991) Expression of immunomolecules on microglial cells following neonatal sciatic nerve axotomy. J Neuroimmunol 35:21–30

    Google Scholar 

  23. Morioka T, Kalehua AN, Streit WJ (1991) Progressive expression of immunomolecules on microglial cells in rat dorsal hippocampus following transient forebrain ischemia. Acta Neuropathol 83: 149–157

    Google Scholar 

  24. Morioka T, Baba T, Black KL, Streit WJ (1991) Response of microglial cells to experimental rat glioma. Glia (in press)

  25. Morris CS, Esiri MM (1991) Immunocytochemical study of macrophages and microglial cells and extracellular matrix components in human CNS disease. 1. Gliomas. J Neurol Sci 101:47–58

    Google Scholar 

  26. Paine JT, Handa H, Yamasaki T, Yamashita J, Miyatake S (1986) Immunohistochemical analysis of infiltrating lymphocytes in central nervous system tumors. Neurosurgery 18:766–772

    Google Scholar 

  27. Racke MK, Dhib-Jalbut S, Cannella B, Albert PS, Raine CS, McFarlin DE (1991) Prevention and treatment of chronic relapsing experimental allergic encephalitis by transforming growth factor 597-1. J Immunol 146:3012–3017

    Google Scholar 

  28. Ranges GE, Figari IS, Espevik T, Palladino MA Jr (1987) Inhibition of cytotoxic T cell development by transforming growth factor β and reversal by recombinant tumor necrosis factor α. J Exp Med 166:991–998

    Google Scholar 

  29. Robinson AP, White TM, Mason DW (1986) Macrophage heterogeneity in the rat as delineated by two monoclonal antibodies MRC OX-41 and MRC OX-42, the latter recognizing complement receptor type 3. Immunology 57:239–247

    Google Scholar 

  30. Rossi ML, Hughes JT, Esiri MM, Coakham HB, Brownell DB (1987) Immunohistological study of mononuclear cell infiltrate in malignant gliomas. Acta Neuropathol (Berl) 74:269–277

    Google Scholar 

  31. Rossi ML, Jones NR, Candy E, Nicoll JAR, Compton JS, Hughes JT, Esiri MM, Moss TH, Cruz-Sanchez FF, Coakham HB (1989) The mononuclear cell infiltrate compared with survival in high-grade astrocytomas. Acta Neuropathol 78:189–193

    Google Scholar 

  32. Schluesener HJ (1990) Transforming growth factors type 597-2 and 597-3 suppress rat astrocyte autoantigen presentation and antagonize hyperinduction of class II major histocompatibility complex antigen expression by interferon-γ and tumor necrosis factor-α. J Neuroimmunol 27:41–47

    Google Scholar 

  33. Shinonaga M, Chang CC, Suzuki N, Sato M, Kuwabara T (1988) Immunohistological evaluation of macrophage infiltrates in brain tumors: correlation with peritumoral edema. J Neurosurg 68:259–265

    Google Scholar 

  34. Stavrou D, Anzil AP, Weidenbach W, Rodt H (1977) Immunofluorescence study of lymphocytic infiltration in gliomas. J Neurol Sci 33:275–282

    Google Scholar 

  35. Stevens A, Klöter I, Roggendorf W (1988) Inflammatory infiltrates and natural killer cell presence in human brain tumors. Cancer 61:738–743

    Google Scholar 

  36. Streit WJ, Graeber MB, Kreutzberg GW (1989) Expression of Ia antigens on perivascular and microglial cells after sublethal and lethal neuronal injury. Exp Neurol 105:115–126

    Google Scholar 

  37. Takeuchi J, Barnard RO (1976) Perivascular lymphocytic cuffing in astrocytomas. Acta Neuropathol (Berl) 35:265–271

    Google Scholar 

  38. Tsunawaki S, Sporn M, Ding A, Nathan C (1988) Deactivation of macrophages by transforming growth factor-β. Nature 334:260–262

    Google Scholar 

  39. von Hanwehr RI, Hofman FM, Taylor CR, Apuzzo MLJ (1984) Mononuclear lymphoid populations infiltrating the microenvironment of primary CNS tumors. J Neurosurg 60:1138–1147

    Google Scholar 

  40. Woollett GR, Barclay AN, Puklavec M, Williams AF (1985) Molecular and antigenic heterogeneity of the rat leukocytecommon antigen from thymocytes and T and B lymphocytes. Eur J Immunol 15:168–173

    Google Scholar 

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Supported in part by an American Cancer Society Institutional Research Grant at the University of Florida

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Morioka, T., Baba, T., Black, K.L. et al. Immunophenotypic analysis of infiltrating leukocytes and microglia in an experimental rat glioma. Acta Neuropathol 83, 590–597 (1992). https://doi.org/10.1007/BF00299407

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  • DOI: https://doi.org/10.1007/BF00299407

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