Microglia Induce CD4 T Lymphocyte Final Effector Function and Death

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 1996 Nov 1

PMID 8920862

Citations 64

Authors

A L Ford

E Foulcher

F A Lemckert

J D Sedgwick

Affiliations

Soon will be listed here.

Abstract

Microglia, a type of tissue macrophage, are the only cells in the central nervous system (CNS) parenchyma to express some major histocompatibility complex (MHC) class II constitutively or to upregulate expression readily. They are thought to play a role in CD4 T cell activation in autoimmune diseases such as multiple sclerosis, as well as in neurodegenerative conditions, Alzheimer's disease in particular. We show here that highly purified MHC class II+ microglia when tested directly ex vivo do indeed support an effector response by an encephalitogenic myelin basic protein-reactive CD4 T cell line from which production of the proinflammatory cytokines, interferon gamma and tumor necrosis factor, is elicited, but not interleukin (IL)-2 secretion or proliferation. After this interaction, the T cells die by apoptosis. Other nonmicroglial but CNS-associated macrophages isolated in parallel stimulate full T cell activation, including IL-2 production, proliferation, and support T cell survival. Neither CNS-derived population expresses B7.1/B7.2. Resident macrophages that terminate effector T cells in tissues constitute a novel and broadly applicable regulatory measure of particular relevance to processes of self-tolerance against sequestered antigens.

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References

Hickey W, Kimura H . Graft-vs.-host disease elicits expression of class I and class II histocompatibility antigens and the presence of scattered T lymphocytes in rat central nervous system. Proc Natl Acad Sci U S A. 1987; 84(7):2082-6. PMC: 304589. DOI: 10.1073/pnas.84.7.2082. View

Bauer J, Wekerle H, Lassmann H . Apoptosis in brain-specific autoimmune disease. Curr Opin Immunol. 1995; 7(6):839-43. PMC: 7135830. DOI: 10.1016/0952-7915(95)80057-3. View

Parish C, Liew F . Immune response to chemically modified flagellin. 3. Enhanced cell-mediated immunity during high and low zone antibody tolerance to flagellin. J Exp Med. 1972; 135(2):298-311. PMC: 2180527. DOI: 10.1084/jem.135.2.298. View

Hunt S, FOWLER M . A repopulation assay for B and T lymphocyte stem cells employing radiation chimaeras. Cell Tissue Kinet. 1981; 14(4):445-64. DOI: 10.1111/j.1365-2184.1981.tb00551.x. View

Boux H, Raison R, Walker K, MUSGROVE E, Basten A . The surface expression of a tumor-associated antigen on human kappa myeloma cells. Eur J Immunol. 1984; 14(3):216-22. DOI: 10.1002/eji.1830140304. View

Matsumoto Y, Hara N, Tanaka R, Fujiwara M . Immunohistochemical analysis of the rat central nervous system during experimental allergic encephalomyelitis, with special reference to Ia-positive cells with dendritic morphology. J Immunol. 1986; 136(10):3668-76. View

Woodroofe M, Bellamy A, Feldmann M, Davison A, Cuzner M . Immunocytochemical characterisation of the immune reaction in the central nervous system in multiple sclerosis. Possible role for microglia in lesion growth. J Neurol Sci. 1986; 74(2-3):135-52. DOI: 10.1016/0022-510x(86)90100-0. View

Espevik T, Nissen-Meyer J . A highly sensitive cell line, WEHI 164 clone 13, for measuring cytotoxic factor/tumor necrosis factor from human monocytes. J Immunol Methods. 1986; 95(1):99-105. DOI: 10.1016/0022-1759(86)90322-4. View

Jenkins M, Schwartz R . Antigen presentation by chemically modified splenocytes induces antigen-specific T cell unresponsiveness in vitro and in vivo. J Exp Med. 1987; 165(2):302-19. PMC: 2188516. DOI: 10.1084/jem.165.2.302. View

10.

Sedgwick J, Brostoff S, Mason D . Experimental allergic encephalomyelitis in the absence of a classical delayed-type hypersensitivity reaction. Severe paralytic disease correlates with the presence of interleukin 2 receptor-positive cells infiltrating the central nervous system. J Exp Med. 1987; 165(4):1058-75. PMC: 2188572. DOI: 10.1084/jem.165.4.1058. View

11.

Paterson D, Jefferies W, Green J, Brandon M, Corthesy P, Puklavec M . Antigens of activated rat T lymphocytes including a molecule of 50,000 Mr detected only on CD4 positive T blasts. Mol Immunol. 1987; 24(12):1281-90. DOI: 10.1016/0161-5890(87)90122-2. View

12.

Hunig T, Wallny H, Hartley J, Lawetzky A, Tiefenthaler G . A monoclonal antibody to a constant determinant of the rat T cell antigen receptor that induces T cell activation. Differential reactivity with subsets of immature and mature T lymphocytes. J Exp Med. 1989; 169(1):73-86. PMC: 2189202. DOI: 10.1084/jem.169.1.73. View

13.

Perry V, Gordon S . Macrophages and microglia in the nervous system. Trends Neurosci. 1988; 11(6):273-7. DOI: 10.1016/0166-2236(88)90110-5. View

14.

Sedgwick J, MacPhee I, Puklavec M . Isolation of encephalitogenic CD4+ T cell clones in the rat. Cloning methodology and interferon-gamma secretion. J Immunol Methods. 1989; 121(2):185-96. DOI: 10.1016/0022-1759(89)90159-2. View

15.

Mattiace L, Davies P, Dickson D . Detection of HLA-DR on microglia in the human brain is a function of both clinical and technical factors. Am J Pathol. 1990; 136(5):1101-14. PMC: 1877424. View

16.

Voorthuis J, Uitdehaag B, de Groot C, Goede P, van der Meide P, Dijkstra C . Suppression of experimental allergic encephalomyelitis by intraventricular administration of interferon-gamma in Lewis rats. Clin Exp Immunol. 1990; 81(2):183-8. PMC: 1535058. DOI: 10.1111/j.1365-2249.1990.tb03315.x. View

17.

Styren S, CIVIN W, Rogers J . Molecular, cellular, and pathologic characterization of HLA-DR immunoreactivity in normal elderly and Alzheimer's disease brain. Exp Neurol. 1990; 110(1):93-104. DOI: 10.1016/0014-4886(90)90054-v. View

18.

Sedgwick J, Mossner R, Schwender S, Ter Meulen V . Major histocompatibility complex-expressing 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. 1991; 173(5):1235-46. PMC: 2118852. DOI: 10.1084/jem.173.5.1235. View

19.

Sedgwick J, Schwender S, Imrich H, Dorries R, Butcher G, Ter Meulen V . Isolation and direct characterization of resident microglial cells from the normal and inflamed central nervous system. Proc Natl Acad Sci U S A. 1991; 88(16):7438-42. PMC: 52311. DOI: 10.1073/pnas.88.16.7438. View

20.

Pender M, Nguyen K, McCombe P, KERR J . Apoptosis in the nervous system in experimental allergic encephalomyelitis. J Neurol Sci. 1991; 104(1):81-7. DOI: 10.1016/0022-510x(91)90219-w. View