Expression of costimulatory molecules B7-1 (CD80), B7-2 (CD86), and interleukin 12 cytokine in multiple sclerosis lesions

doi:10.1084/jem.182.6.1985

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Expression of costimulatory molecules B7-1 (CD80), B7-2 (CD86), and interleukin 12 cytokine in multiple sclerosis lesions

A Windhagen, J Newcombe, F Dangond, C Strand, MN Woodroofe, ML Cuzner and DA Hafler
Laboratory of Molecular Immunology, Brigham and Women's Hospital, Boston, Massachusetts, USA.

Resting autoreactive T cells are present in the circulation of normal individuals without pathologic consequences. In autoimmune animal models, stimulation of these self-reactive T cells in the presence of costimulatory molecules B7-1 results in T cell-mediated autoimmune disease, whereas B7-2 stimulation generates regulatory autoreactive T cells that abrogate disease severity. Thus, reactivation in the brain of myelin-autoreactive T cells by antigen with costimulatory molecules may be a critical event in the pathophysiology of multiple sclerosis (MS), a putative autoimmune disease of central nervous system (CNS) myelin. We investigated the expression of cytokines and costimulatory molecules in a panel of 41 histologically characterized CNS specimens from 15 MS and 10 control cases using semiquantitative reverse transcriptase-polymerase chain reaction and immunocytochemistry. In four cases, vascular CNS infarcts with inflammation were compared with MS plaques from the same brain. We observed increased expression of B7- 1 and interleukin (IL) 12p40 in acute MS plaques, particularly from early disease cases but not in inflammatory infarcts. B7-1 staining was localized predominantly to the lymphocytes in perivenular inflammatory cuffs but not the parenchyma. In contrast, B7-2 was expressed predominantly on macrophages both in MS lesions of varied time duration and in inflammatory infarcts. These findings indicate that an early event in the initiation of MS involves upregulation of B7-1 and IL-12, resulting in conditions that maximally stimulate T cell activation and induction of T helper 1-type immune responses.
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Sloka, J S, Stefanelli, M (2005). The mechanism of action of methylprednisolone in the treatment of multiple sclerosis. Mult Scler 11: 425-432 [Abstract]
Huang, Y.-M., Liu, X., Steffensen, K., Sanna, A., Arru, G., Fois, M. L., Rosati, G., Sotgiu, S., Link, H. (2005). Immunological heterogeneity of multiple sclerosis in Sardinia and Sweden. Mult Scler 11: 16-23 [Abstract]
Weiner, H. L. (2004). Multiple Sclerosis Is an Inflammatory T-Cell-Mediated Autoimmune Disease. Arch Neurol 61: 1613-1615 [Full Text]
Hofer, M., Hausmann, J., Staeheli, P., Pagenstecher, A. (2004). Cerebral Expression of Interleukin-12 Induces Neurological Disease via Differential Pathways and Recruits Antigen-Specific T Cells in Virus-Infected Mice. Am. J. Pathol. 165: 949-958 [Abstract] [Full Text]
Zoukos, Y, Thomaides, T N, Kidd, D, Cuzner, M L, Thompson, A (2003). Expression of {beta}2 adrenoreceptors on peripheral blood mononuclear cells in patients with primary and secondary progressive multiple sclerosis: a longitudinal six month study. J. Neurol. Neurosurg. Psychiatry 74: 197-202 [Abstract] [Full Text]
De Keyser, J., Zeinstra, E., Frohman, E. (2003). Are Astrocytes Central Players in the Pathophysiology of Multiple Sclerosis?. Arch Neurol 60: 132-136 [Abstract] [Full Text]
Brok, H. P. M., van Meurs, M., Blezer, E., Schantz, A., Peritt, D., Treacy, G., Laman, J. D., Bauer, J., 't Hart, B. A. (2002). Prevention of Experimental Autoimmune Encephalomyelitis in Common Marmosets Using an Anti-IL-12p40 Monoclonal Antibody. J. Immunol. 169: 6554-6563 [Abstract] [Full Text]
Freude, S., Hausmann, J., Hofer, M., Pham-Mitchell, N., Campbell, I. L., Staeheli, P., Pagenstecher, A. (2002). Borna Disease Virus Accelerates Inflammation and Disease Associated with Transgenic Expression of Interleukin-12 in the Central Nervous System. J. Virol. 76: 12223-12232 [Abstract] [Full Text]
Ozenci, V, Kouwenhoven, M, Link, H (2002). Cytokines in multiple sclerosis: methodological aspects and pathogenic implications. Mult Scler 8: 396-404 [Abstract]
Kim, J., Ochoa, M.-T., Krutzik, S. R., Takeuchi, O., Uematsu, S., Legaspi, A. J., Brightbill, H. D., Holland, D., Cunliffe, W. J., Akira, S., Sieling, P. A., Godowski, P. J., Modlin, R. L. (2002). Activation of Toll-Like Receptor 2 in Acne Triggers Inflammatory Cytokine Responses. J. Immunol. 169: 1535-1541 [Abstract] [Full Text]
Sugerman, P.B., Savage, N.W., Walsh, L.J., Zhao, Z.Z., Zhou, X.J., Khan, A., Seymour, G.J., Bigby, M. (2002). THE PATHOGENESIS OF ORAL LICHEN PLANUS. CROBM 13: 350-365 [Abstract] [Full Text]
Lassmann, S., Kincaid, C., Asensio, V. C., Campbell, I. L. (2001). Induction of Type 1 Immune Pathology in the Brain Following Immunization Without Central Nervous System Autoantigen in Transgenic Mice With Astrocyte-Targeted Expression of IL-12. J. Immunol. 167: 5485-5493 [Abstract] [Full Text]
Liu, Z., Geboes, K., Hellings, P., Maerten, P., Heremans, H., Vandenberghe, P., Boon, L., van Kooten, P., Rutgeerts, P., Ceuppens, J. L. (2001). B7 Interactions with CD28 and CTLA-4 Control Tolerance or Induction of Mucosal Inflammation in Chronic Experimental Colitis. J. Immunol. 167: 1830-1838 [Abstract] [Full Text]
Gonnella, P. A., Waldner, H. P., Weiner, H. L. (2001). B Cell-Deficient ({micro}MT) Mice Have Alterations in the Cytokine Microenvironment of the Gut-Associated Lymphoid Tissue (GALT) and a Defect in the Low Dose Mechanism of Oral Tolerance. J. Immunol. 166: 4456-4464 [Abstract] [Full Text]
Huang, D., Wang, J., Kivisakk, P., Rollins, B. J., Ransohoff, R. M. (2001). Absence of Monocyte Chemoattractant Protein 1 in Mice Leads to Decreased Local Macrophage Recruitment and Antigen-Specific T Helper Cell Type 1 Immune Response in Experimental Autoimmune Encephalomyelitis. JEM 193: 713-726 [Abstract] [Full Text]
Calida, D. M., Constantinescu, C., Purev, E., Zhang, G.-X., Ventura, E. S., Lavi, E., Rostami, A. (2001). Cutting Edge: C3, a Key Component of Complement Activation, Is Not Required for the Development of Myelin Oligodendrocyte Glycoprotein Peptide-Induced Experimental Autoimmune Encephalomyelitis in Mice. J. Immunol. 166: 723-726 [Abstract] [Full Text]
Lassmann, H. (2000). The New Pathology of Multiple Sclerosis. Mult Scler 6: 409-410
Katz-Levy, Y., Neville, K. L., Padilla, J., Rahbe, S., Begolka, W. S., Girvin, A. M., Olson, J. K., Vanderlugt, C. L., Miller, S. D. (2000). Temporal Development of Autoreactive Th1 Responses and Endogenous Presentation of Self Myelin Epitopes by Central Nervous System-Resident APCs in Theiler's Virus-Infected Mice. J. Immunol. 165: 5304-5314 [Abstract] [Full Text]
Neville, K. L., Dal Canto, M. C., Bluestone, J. A., Miller, S. D. (2000). CD28 Costimulatory Blockade Exacerbates Disease Severity and Accelerates Epitope Spreading in a Virus-Induced Autoimmune Disease. J. Virol. 74: 8349-8357 [Abstract] [Full Text]
Kiefer, R, Dangond, F, Mueller, M, Toyka, K V, Hafler, D A, Hartung, H-P (2000). Enhanced B7 costimulatory molecule expression in inflammatory human sural nerve biopsies. J. Neurol. Neurosurg. Psychiatry 69: 362-368 [Abstract] [Full Text]
Wandinger, K.-P., Jabs, W., Siekhaus, A., Bubel, S., Trillenberg, P., Wagner, H.-J., Wessel, K., Kirchner, H., Hennig, H. (2000). Association between clinical disease activity and Epstein-Barr virus reactivation in MS. Neurology 55: 178-184 [Abstract] [Full Text]
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Bajramovic, J. J., Plomp, A. C., Goes, A. v. d., Koevoets, C., Newcombe, J., Cuzner, M. L., van Noort, J. M. (2000). Presentation of {alpha}B-Crystallin to T Cells in Active Multiple Sclerosis Lesions: An Early Event Following Inflammatory Demyelination. J. Immunol. 164: 4359-4366 [Abstract] [Full Text]
Inoue, A., Koh, C.-S., Yamazaki, M., Yagita, H. (1999). Effect of Anti-B7-1 and Anti-B7-2 mAb on Theiler's Murine Encephalomyelitis Virus-Induced Demyelinating Disease. J. Immunol. 163: 6180-6186 [Abstract] [Full Text]
Reichmann, G., Villegas, E. N., Craig, L., Peach, R., Hunter, C. A. (1999). The CD28/B7 Interaction Is Not Required for Resistance to Toxoplasma gondii in the Brain but Contributes to the Development of Immunopathology. J. Immunol. 163: 3354-3362 [Abstract] [Full Text]
Soos, J. M., Ashley, T. A., Morrow, J., Patarroyo, J. C., Szente, B. E., Zamvil, S. S. (1999). Differential expression of B7 co-stimulatory molecules by astrocytes correlates with T cell activation and cytokine production. Int Immunol 11: 1169-1179 [Abstract] [Full Text]
Cowdery, J. S., Boerth, N. J., Norian, L. A., Myung, P. S., Koretzky, G. A. (1999). Differential Regulation of the IL-12 p40 Promoter and of p40 Secretion by CpG DNA and Lipopolysaccharide. J. Immunol. 162: 6770-6775 [Abstract] [Full Text]
Oliveira-dos-Santos, A. J., Ho, A., Tada, Y., Lafaille, J. J., Tonegawa, S., Mak, T. W., Penninger, J. M. (1999). CD28 Costimulation Is Crucial for the Development of Spontaneous Autoimmune Encephalomyelitis. J. Immunol. 162: 4490-4495 [Abstract] [Full Text]
Zou, J.-P., Morford, L. A., Chougnet, C., Dix, A. R., Brooks, A. G., Torres, N., Shuman, J. D., Coligan, J. E., Brooks, W. H., Roszman, T. L., Shearer, G. M. (1999). Human Glioma-Induced Immunosuppression Involves Soluble Factor(s) That Alters Monocyte Cytokine Profile and Surface Markers. J. Immunol. 162: 4882-4892 [Abstract] [Full Text]
Poggi, A., Zocchi, M. R., Costa, P., Ferrero, E., Borsellino, G., Placido, R., Galgani, S., Salvetti, M., Gasperini, C., Ristori, G., Brosnan, C. F., Battistini, L. (1999). IL-12-Mediated NKRP1A Up-Regulation and Consequent Enhancement of Endothelial Transmigration of V{delta}2+ TCR{gamma}{delta}+ T Lymphocytes from Healthy Donors and Multiple Sclerosis Patients. J. Immunol. 162: 4349-4354 [Abstract] [Full Text]
Clark, L. B., Appleby, M. W., Brunkow, M. E., Wilkinson, J. E., Ziegler, S. F., Ramsdell, F. (1999). Cellular and Molecular Characterization of the scurfy Mouse Mutant. J. Immunol. 162: 2546-2554 [Abstract] [Full Text]
Aloisi, F., Penna, G., Polazzi, E., Minghetti, L., Adorini, L. (1999). CD40-CD154 Interaction and IFN-{gamma} Are Required for IL-12 But Not Prostaglandin E2 Secretion by Microglia During Antigen Presentation to Th1 Cells. J. Immunol. 162: 1384-1391 [Abstract] [Full Text]
Peterson, K. E., Sharp, G. C., Tang, H., Braley-Mullen, H. (1999). B7.2 Has Opposing Roles During the Activation Versus Effector Stages of Experimental Autoimmune Thyroiditis. J. Immunol. 162: 1859-1867 [Abstract] [Full Text]
Bright, J. J., Du, C., Coon, M., Sriram, S., Klaus, S. J. (1998). Prevention of Experimental Allergic Encephalomyelitis via Inhibition of IL-12 Signaling and IL-12-Mediated Th1 Differentiation: An Effect of the Novel Anti-Inflammatory Drug Lisofylline. J. Immunol. 161: 7015-7022 [Abstract] [Full Text]
Battifora, M., Pesce, G., Paolieri, F., Fiorino, N., Giordano, C., Riccio, A. M., Torre, G., Olive, D., Bagnasco, M. (1998). B7.1 Costimulatory Molecule Is Expressed on Thyroid Follicular Cells in Hashimoto's Thyroiditis, But Not in Graves' Disease. J. Clin. Endocrinol. Metab. 83: 4130-4139 [Abstract] [Full Text]
Pope, J. G., Vanderlugt, C. L., Rahbe, S. M., Lipton, H. L., Miller, S. D. (1998). Characterization of and Functional Antigen Presentation by Central Nervous System Mononuclear Cells from Mice Infected with Theiler's Murine Encephalomyelitis Virus. J. Virol. 72: 7762-7771 [Abstract] [Full Text]
Tran, E. H., Hoekstra, K., van Rooijen, N., Dijkstra, C. D., Owens, T. (1998). Immune Invasion of the Central Nervous System Parenchyma and Experimental Allergic Encephalomyelitis, But Not Leukocyte Extravasation from Blood, Are Prevented in Macrophage-Depleted Mice. J. Immunol. 161: 3767-3775 [Abstract] [Full Text]
Bright, J. J., Sriram, S. (1998). TGF-{beta} Inhibits IL-12-Induced Activation of Jak-STAT Pathway in T Lymphocytes. J. Immunol. 161: 1772-1777 [Abstract] [Full Text]
Karandikar, N. J., Vanderlugt, C. L., Eagar, T., Tan, L., Bluestone, J. A., Miller, S. D. (1998). Tissue-Specific Up-Regulation of B7-1 Expression and Function During the Course of Murine Relapsing Experimental Autoimmune Encephalomyelitis. J. Immunol. 161: 192-199 [Abstract] [Full Text]
Chen, H., Hendricks, R. L. (1998). B7 Costimulatory Requirements of T Cells at an Inflammatory Site. J. Immunol. 160: 5045-5052 [Abstract] [Full Text]
Ushio, H., Tsuji, R. F., Szczepanik, M., Kawamoto, K., Matsuda, H., Askenase, P. W. (1998). IL-12 Reverses Established Antigen-Specific Tolerance of Contact Sensitivity by Affecting Costimulatory Molecules B7-1 (CD80) and B7-2 (CD86). J. Immunol. 160: 2080-2088 [Abstract] [Full Text]
Ferrante, P., Fusi, M. L., Saresella, M., Caputo, D., Biasin, M., Trabattoni, D., Salvaggio, A., Clerici, E., de Vries, J. E., Aversa, G., Cazzullo, C. L., Clerici, M. (1998). Cytokine Production and Surface Marker Expression in Acute and Stable Multiple Sclerosis: Altered IL-12 Production and Augmented Signaling Lymphocytic Activation Molecule (SLAM)-Expressing Lymphocytes in Acute Multiple Sclerosis. J. Immunol. 160: 1514-1521 [Abstract] [Full Text]
Scholz, C., Patton, K. T., Anderson, D. E., Freeman, G. J., Hafler, D. A. (1998). Expansion of Autoreactive T Cells in Multiple Sclerosis Is Independent of Exogenous B7 Costimulation. J. Immunol. 160: 1532-1538 [Abstract] [Full Text]
Smith, D. R., Weiner, H. L. (1997). Immunologic Aspects of Neurologic and Neuromuscular Diseases. JAMA 278: 1956-1961 [Abstract]
Parijs, L. V., Perez, V. L., Biuckians, A., Maki, R. G., London, C. A., Abbas, A. K. (1997). Role of Interleukin 12 and Costimulators in T Cell Anergy In Vivo. JEM 186: 1119-1128 [Abstract] [Full Text]
Becker, K. J., McCarron, R. M., Ruetzler, C., Laban, O., Sternberg, E., Flanders, K. C., Hallenbeck, J. M. (1997). Immunologic tolerance to myelin basic protein decreases stroke size after transient focal�cerebral�ischemia. Proc. Natl. Acad. Sci. USA 94: 10873-10878 [Abstract] [Full Text]
Richardson, J.H., Hollsberg, P., Windhagen, A., Child, L.A., Hafler, D.A., Lever, A.M.L. (1997). Variable Immortalizing Potential and Frequent Virus Latency in Blood-Derived T-Cell Clones Infected With Human T-Cell Leukemia Virus Type I. Blood 89: 3303-3314 [Abstract] [Full Text]
Balashov, K.�E., Smith, D.�R., Khoury, S.�J., Hafler, D.�A., Weiner, H.�L. (1997). Increased interleukin 12�production in progressive multiple sclerosis: Induction by activated CD4+ T cells via CD40�ligand. Proc. Natl. Acad. Sci. USA 94: 599-603 [Abstract] [Full Text]
Wolf, S. D., Dittel, B. N., Hardardottir, F., Janeway, C. A. Jr. (1996). Experimental Autoimmune Encephalomyelitis Induction in Genetically B Cell-deficient Mice. JEM 184: 2271-2278 [Abstract] [Full Text]
(1996). Meeting Report and Proceedings: Multiple Sclerosis Society of Great Britain and Northern Ireland. Mult Scler 2: 1-55