Opioid growth factor and low-dose naltrexone impair central nervous system infiltration by CD4 + T lymphocytes in established experimental autoimmune encephalomyelitis, a model of multiple sclerosis.

Abstract

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS), characterized by infiltrating myelin-reactive T lymphocytes and demyelinating lesions. Experimental autoimmune encephalomyelitis (EAE) is the animal model widely utilized to study MS. EAE is mediated by CD4(+) T cells and can be induced in EAE-susceptible mice through immunization with a myelin antigen, such as proteolipid protein 139-151 (PLP139-151) in SJL mice. In this PLP-induced EAE model, autoreactive CD4(+) T cells migrate from peripheral tissues into the CNS where they are reactivated resulting in CNS damage. Th1 and Th17 cells produce the pro-inflammatory cytokines IFNγ and IL-17, respectively, that have been shown to have pathogenic roles in EAE and MS. Anti-inflammatory Th2, IL-4 secreting cells, have been indicated to inhibit EAE exacerbation. However, given the inflammatory environment of EAE, Th2 effector cells are outnumbered by Th1/Th17 cells. Regulatory CD4(+) T cells suppress immune reactions and have been demonstrated to be dysfunctional in MS patients. Opioid growth factor (OGF), chemically termed [Met(5)]-enkephalin, is a negative growth factor that interacts with the OGF receptor. The OGF-OGFr axis can be activated through exogenous administration of OGF or a low dosage of naltrexone (LDN), an opioid antagonist. We have previously demonstrated that modulation of the OGF-OGFr axis results in alleviation from relapse-remitting EAE, and that CNS-infiltrating CD3(+) T cells are diminished with exogenous OGF or intermittent blockade with LDN administration. In this paper, we aimed to determine whether OGF or LDN alter the Th effector responses of CD4(+) T lymphocytes within the CNS in established EAE. We report in these studies that the numbers of CD4(+) T lymphocytes in the CNS of EAE mice are decreased following treatment with OGF for five days but not LDN. However, modulation of the OGF-OGFr axis did not result in changes to CD4(+) Th effector cell responses in the CNS of EAE mice.

• Authors: Leslie A Hammer, Hanspeter Waldner, Ian S Zagon, Patricia J McLaughlin
• Journal: Experimental biology and medicine (Maywood, N.J.) (Exp Biol Med (Maywood)) Vol. 241 Issue 1 Pg. 71-8 (Jan 2016) ISSN: 1535-3699 [Electronic] England
• PMID: 26202376 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2016 by the Society for Experimental Biology and Medicine.

Chemical References

• Narcotic Antagonists
• Enkephalin, Methionine
• Naltrexone

Topics

• Animals
• CD4-Positive T-Lymphocytes (immunology)
• Central Nervous System (pathology)
• Disease Models, Animal
• Encephalomyelitis, Autoimmune, Experimental (pathology)
• Enkephalin, Methionine (administration & dosage)
• Female
• Mice
• Multiple Sclerosis (pathology)
• Naltrexone (administration & dosage)
• Narcotic Antagonists (administration & dosage)