Tags

Type your tag names separated by a space and hit enter

Tumor necrosis factor blockade in actively induced experimental autoimmune encephalomyelitis prevents clinical disease despite activated T cell infiltration to the central nervous system.
Eur J Immunol. 1997 Aug; 27(8):1973-81.EJ

Abstract

Recently, we demonstrated that experimental autoimmune encephalomyelitis (EAE) in the rat, passively transferred using myelin basic protein (MBP)-reactive encephalitogenic CD4+ T cells, was preventable by administration of a p55-tumor necrosis factor-IgG fusion protein (TNFR-IgG). This was despite quantitatively and qualitatively normal movement of these MBP-specific T cells to the central nervous system (CNS). To extend these findings, the effect of TNFR-IgG on EAE actively induced by injection of MBP in complete Freund's adjuvant was examined. This form of EAE in the rat typically involves an acute, self-limiting neurological deficit, substantial CNS inflammation, but minimal demyelination. Here we show that administration of TNFR-IgG prior to onset of disease signs completely prevented the neurological deficit or markedly reduced its severity. This blockade of clinical disease was dissociated from weight loss which occurred at the same tempo and magnitude as in control rats exhibiting neurological signs of disease such as paralysis. The timing of TNF blockade was critical as established clinical disease was relatively refractory to TNFR-IgG treatment. Activated CD4+ T cells expressing normal or elevated levels of VLA4, major histocompatibility complex class II, MRC OX40 and CD25 were isolated from or immunohistochemically localized in the CNS of clinically healthy rats treated before disease onset. There was a reduction of the amount of other inflammatory leukocytes in the CNS of these treated animals but, more importantly, the activation state of inflammatory leukocytes, as well as that of microglia isolated from treated animals, was reduced. Thus, TNFR-IgG, when administered before disease onset, appears to act by inhibiting an effector function of activated T cells and possibly other inflammatory leukocytes necessary to bring about the neurological deficit. However, while TNF is a critically important cytokine for the early events leading to initiation of EAE, it is not a necessary factor in the acute neurological deficit characteristic of this form of EAE, once disease onset has occurred.

Authors+Show Affiliations

Centenary Institute of Cancer Medicine and Cell Biology, Royal Prince Alfred Hospital, Sydney, NSW, Australia.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

Language

eng

PubMed ID

9295034

Citation

Körner, H, et al. "Tumor Necrosis Factor Blockade in Actively Induced Experimental Autoimmune Encephalomyelitis Prevents Clinical Disease Despite Activated T Cell Infiltration to the Central Nervous System." European Journal of Immunology, vol. 27, no. 8, 1997, pp. 1973-81.
Körner H, Lemckert FA, Chaudhri G, et al. Tumor necrosis factor blockade in actively induced experimental autoimmune encephalomyelitis prevents clinical disease despite activated T cell infiltration to the central nervous system. Eur J Immunol. 1997;27(8):1973-81.
Körner, H., Lemckert, F. A., Chaudhri, G., Etteldorf, S., & Sedgwick, J. D. (1997). Tumor necrosis factor blockade in actively induced experimental autoimmune encephalomyelitis prevents clinical disease despite activated T cell infiltration to the central nervous system. European Journal of Immunology, 27(8), 1973-81.
Körner H, et al. Tumor Necrosis Factor Blockade in Actively Induced Experimental Autoimmune Encephalomyelitis Prevents Clinical Disease Despite Activated T Cell Infiltration to the Central Nervous System. Eur J Immunol. 1997;27(8):1973-81. PubMed PMID: 9295034.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Tumor necrosis factor blockade in actively induced experimental autoimmune encephalomyelitis prevents clinical disease despite activated T cell infiltration to the central nervous system. AU - Körner,H, AU - Lemckert,F A, AU - Chaudhri,G, AU - Etteldorf,S, AU - Sedgwick,J D, PY - 1997/8/1/pubmed PY - 1997/9/19/medline PY - 1997/8/1/entrez SP - 1973 EP - 81 JF - European journal of immunology JO - Eur J Immunol VL - 27 IS - 8 N2 - Recently, we demonstrated that experimental autoimmune encephalomyelitis (EAE) in the rat, passively transferred using myelin basic protein (MBP)-reactive encephalitogenic CD4+ T cells, was preventable by administration of a p55-tumor necrosis factor-IgG fusion protein (TNFR-IgG). This was despite quantitatively and qualitatively normal movement of these MBP-specific T cells to the central nervous system (CNS). To extend these findings, the effect of TNFR-IgG on EAE actively induced by injection of MBP in complete Freund's adjuvant was examined. This form of EAE in the rat typically involves an acute, self-limiting neurological deficit, substantial CNS inflammation, but minimal demyelination. Here we show that administration of TNFR-IgG prior to onset of disease signs completely prevented the neurological deficit or markedly reduced its severity. This blockade of clinical disease was dissociated from weight loss which occurred at the same tempo and magnitude as in control rats exhibiting neurological signs of disease such as paralysis. The timing of TNF blockade was critical as established clinical disease was relatively refractory to TNFR-IgG treatment. Activated CD4+ T cells expressing normal or elevated levels of VLA4, major histocompatibility complex class II, MRC OX40 and CD25 were isolated from or immunohistochemically localized in the CNS of clinically healthy rats treated before disease onset. There was a reduction of the amount of other inflammatory leukocytes in the CNS of these treated animals but, more importantly, the activation state of inflammatory leukocytes, as well as that of microglia isolated from treated animals, was reduced. Thus, TNFR-IgG, when administered before disease onset, appears to act by inhibiting an effector function of activated T cells and possibly other inflammatory leukocytes necessary to bring about the neurological deficit. However, while TNF is a critically important cytokine for the early events leading to initiation of EAE, it is not a necessary factor in the acute neurological deficit characteristic of this form of EAE, once disease onset has occurred. SN - 0014-2980 UR - https://www.unboundmedicine.com/medline/citation/9295034/Tumor_necrosis_factor_blockade_in_actively_induced_experimental_autoimmune_encephalomyelitis_prevents_clinical_disease_despite_activated_T_cell_infiltration_to_the_central_nervous_system_ L2 - https://doi.org/10.1002/eji.1830270822 DB - PRIME DP - Unbound Medicine ER -