Endogenous opioid inhibition of proliferation of T and B cell subpopulations in response to immunization for experimental autoimmune encephalomyelitis

BMC Immunology

Ian S Zagon¹  Marcus J Magister¹  Daniel P McHugh¹  Patricia J McLaughlin¹ 

[1] Department of Neural & Behavioral Sciences, Pennsylvania State University College of Medicine, 500 University Drive, Hershey, MC H109, PA, USA

关键词: Multiple sclerosis;    Experimental autoimmune encephalomyelitis;    T cell proliferation;    OGF;    Low dose naltrexone;   

Others  :  1175022
DOI  :  10.1186/s12865-015-0093-0

 received in 2014-12-09, accepted in 2015-04-10,  发布年份 2015

【 摘 要 】

Background

Experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, is induced by immunization of mice with myelin oligodendrocytic glycoprotein (MOG_35-55) injections, and after 9 days, mice develop behavioral signs of chronic progressive EAE. Proliferation of T and B cells located in peripheral lymph tissues such as spleen and inguinal lymph nodes of C57BL/6J mice are stimulated. The opioid growth factor-opioid growth factor receptor (OGF-OGFr) axis has been shown to effectively limit progression of chronic EAE when mice are treated at the time of induction or at time of established disease.In addition to repressed behavioral profiles, spinal cord neuropathology is diminished in mice treated with OGF or low dosages of naltrexone (LDN). However, there is little or no information on peripheral lymphocyte dynamics following immunization of mice with MOG antigen and treatment with OGF or LDN.

Methods

Six-week old female mice were immunized with MOG35-55 and were injected intraperitoneally with OGF or a low dosage of naltrexone (LDN) beginning at the time of immunization; saline-injected immunized mice served as controls. Normal mice received saline for all injections. Periodically over a 2 week period, spleens and inguinal lymph nodes were removed, total lymphocytes counted, and subpopulations of CD4+ and CD8+ specific T-cells, as well as B lymphocytes, were determined by flow cytometry. On day 15 of treatment, lumbar spinal cord tissue was removed; CNS lymphocytes isolated, and assayed for Th1, Th2, and Th17 markers by flow cytometry.

Results

Exogenous OGF or endogenous OGF following LDN suppressed T and B lymphocyte proliferation in the spleen and inguinal lymph nodes of MOG-immunized mice.Suppression of peripheral immune cell CD4+ and CD8+ T cell proliferation at 5 and 12 days correlated with reductions in clinical behavior.EAE mice treated with OGF for 15 days displayed elevated Th1 and Th17 cells; no subpopulations of Th2-specific T cells were noted.

Conclusions

OGF or LDN repress proliferation of CD4+ and CD8+T cells and B220+ B lymphocytes in the spleen and lymph nodes of immunized mice within a week of immunization.These data provide novel mechanistic pathways underlying the efficacy of OGF and LDN therapy for MS.

【 授权许可】

   
2015 McLaughlin et al.; licensee BioMed Central.

【 图 表 】

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