An important role for the chemokine macrophage inflammatory protein-1α in the pathogenesis of the T cell-mediated autoimmune disease, experimental autoimmune encephalomyelitis

W. J. Karpus*, N. W. Lukacs, B. L. McRae, R. M. Strieter, S. L. Kunkel, S. D. Miller

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

457 Scopus citations

Abstract

Experimental autoimmune encephalomyelitis (EAE) is a CD4+ T cell- mediated, inflammatory demyelinating disease of the central nervous system (CNS) that serves as a model for the human demyelinating disease, multiple sclerosis. A critical event in the pathogenesis of EAE is the entry of both Ag-specific T lymphocytes and Ag-nonspecific mononuclear cells into the CNS. In the present report we investigated the role of two C-C chemokines (macrophage inflammatory protein-1α (MIP-1α) and monocyte chemotactic protein-1) and a C-x-C chemokine (MIP-2) in the pathogenesis of EAE. Production in the CNS of MIP-1α, but not that of MIP-2, a rodent homologue of IL-8, or monocyte chemotactic protein-1, correlated with development of severe clinical disease. Administration of anti-MIP-1α, but not thai of anti-monocyte chemotactic protein-1, prevented the development of both acute and relapsing paralytic disease as well as infiltration of mononuclear cells into the CNS initiated by the transfer of neuroantigen peptide-activated T cells. Ab therapy could also be used to ameliorate the severity of ongoing clinical disease. Anti-MIP-1α did not affect the activation of encephalitogenic T cells as measured by cytokine secretion, surface marker expression, and ability to adoptively transfer EAE. These results demonstrate that MIP-1α plays an important role in directing the chemoattraction of mononuclear inflammatory cells in the T cell-mediated autoimmune disease, EAE.

Original languageEnglish (US)
Pages (from-to)5003-5010
Number of pages8
JournalJournal of Immunology
Volume155
Issue number10
StatePublished - 1995

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'An important role for the chemokine macrophage inflammatory protein-1α in the pathogenesis of the T cell-mediated autoimmune disease, experimental autoimmune encephalomyelitis'. Together they form a unique fingerprint.

Cite this