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Kinetics and cellular origin of cytokines in the central nervous system: insight into mechanisms of myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis.
J Immunol. 2000 Jan 01; 164(1):419-26.JI

Abstract

Experimental autoimmune encephalomyelitis induced by myelin oligodendrocyte glycoprotein (MOG) in C57BL/6 (H-2b) mice is characterized by early (day 12) acute paralysis, followed by a sustained chronic clinical course that gradually stabilizes. Extensive inflammation and demyelination coincide with clinical signs of disease. To identify the mechanisms of these processes, individual proinflammatory and anti-inflammatory cytokines and chemokines were studied. Sensitive single-cell assays were utilized to determine the cellular origin and kinetics of cytokine production in the CNS. Immunization with MOG35-55 peptide resulted in priming of both Th1 (lymphotoxin, IFN-gamma, and TNF-alpha) and Th2 (IL-4) cells in the spleen. However, only Th1 cells were apparent in the CNS. CD4 T cells that produced IFN-gamma or TNF-alpha were present in the CNS by day 7 after immunization with MOG35-55, peaked at day 20, and then waned. TNF-alpha was also produced in the CNS by Mac-1+ cells. On days 7 and 10 after immunization, the TNF-alpha-producing Mac1+ cells were predominantly microglia. By day 14, a switch occurred in that the Mac1+ TNF-alpha-producing cells had the phenotype of infiltrating macrophages. RANTES, IFN-inducible protein 10 (IP-10), and monocyte chemotactic protein 1 chemokine mRNA were detected in the CNS by day 8 after immunization. The early presence of monocyte chemotactic protein 1 (MCP-1) in the CNS provides a mechanism for the recruitment of macrophages. These data implicate TNF-alpha production by a continuum of T cells, microglia, and macrophages at various times during the course of disease. The importance of Th1 cytokines is highlighted, with little evidence for a role of Th2 cytokines.

Authors+Show Affiliations

Department of Epidemiology and Public Health, Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

10605038

Citation

Juedes, A E., et al. "Kinetics and Cellular Origin of Cytokines in the Central Nervous System: Insight Into Mechanisms of Myelin Oligodendrocyte Glycoprotein-induced Experimental Autoimmune Encephalomyelitis." Journal of Immunology (Baltimore, Md. : 1950), vol. 164, no. 1, 2000, pp. 419-26.
Juedes AE, Hjelmström P, Bergman CM, et al. Kinetics and cellular origin of cytokines in the central nervous system: insight into mechanisms of myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis. J Immunol. 2000;164(1):419-26.
Juedes, A. E., Hjelmström, P., Bergman, C. M., Neild, A. L., & Ruddle, N. H. (2000). Kinetics and cellular origin of cytokines in the central nervous system: insight into mechanisms of myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis. Journal of Immunology (Baltimore, Md. : 1950), 164(1), 419-26.
Juedes AE, et al. Kinetics and Cellular Origin of Cytokines in the Central Nervous System: Insight Into Mechanisms of Myelin Oligodendrocyte Glycoprotein-induced Experimental Autoimmune Encephalomyelitis. J Immunol. 2000 Jan 1;164(1):419-26. PubMed PMID: 10605038.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Kinetics and cellular origin of cytokines in the central nervous system: insight into mechanisms of myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis. AU - Juedes,A E, AU - Hjelmström,P, AU - Bergman,C M, AU - Neild,A L, AU - Ruddle,N H, PY - 1999/12/22/pubmed PY - 1999/12/22/medline PY - 1999/12/22/entrez SP - 419 EP - 26 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 164 IS - 1 N2 - Experimental autoimmune encephalomyelitis induced by myelin oligodendrocyte glycoprotein (MOG) in C57BL/6 (H-2b) mice is characterized by early (day 12) acute paralysis, followed by a sustained chronic clinical course that gradually stabilizes. Extensive inflammation and demyelination coincide with clinical signs of disease. To identify the mechanisms of these processes, individual proinflammatory and anti-inflammatory cytokines and chemokines were studied. Sensitive single-cell assays were utilized to determine the cellular origin and kinetics of cytokine production in the CNS. Immunization with MOG35-55 peptide resulted in priming of both Th1 (lymphotoxin, IFN-gamma, and TNF-alpha) and Th2 (IL-4) cells in the spleen. However, only Th1 cells were apparent in the CNS. CD4 T cells that produced IFN-gamma or TNF-alpha were present in the CNS by day 7 after immunization with MOG35-55, peaked at day 20, and then waned. TNF-alpha was also produced in the CNS by Mac-1+ cells. On days 7 and 10 after immunization, the TNF-alpha-producing Mac1+ cells were predominantly microglia. By day 14, a switch occurred in that the Mac1+ TNF-alpha-producing cells had the phenotype of infiltrating macrophages. RANTES, IFN-inducible protein 10 (IP-10), and monocyte chemotactic protein 1 chemokine mRNA were detected in the CNS by day 8 after immunization. The early presence of monocyte chemotactic protein 1 (MCP-1) in the CNS provides a mechanism for the recruitment of macrophages. These data implicate TNF-alpha production by a continuum of T cells, microglia, and macrophages at various times during the course of disease. The importance of Th1 cytokines is highlighted, with little evidence for a role of Th2 cytokines. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/10605038/Kinetics_and_cellular_origin_of_cytokines_in_the_central_nervous_system:_insight_into_mechanisms_of_myelin_oligodendrocyte_glycoprotein_induced_experimental_autoimmune_encephalomyelitis_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=10605038 DB - PRIME DP - Unbound Medicine ER -