Inconsistence between number and function of autoreactive T cells in the course of experimental autoimmune encephalomyelitis

ABSTRACT

Background: Mouse experimental autoimmune encephalomyelitis (EAE) is widely used model of multiple sclerosis (MS). The role of autoreactive CD4⁺ and CD8⁺ T cells in the development of mouse EAE has been demonstrated. However, little information is available about the relation between the frequency and reactivity of myelin antigen-reactive CD4⁺ and CD8⁺ T cells in secondary lymphoid organs and their relevance with the inflammation and pathological lesion of CNS during the course of EAE mouse model.

Methods: In this study, an EAE model with a clinical course containing acute onset, peak and chronic remission stages was established in C57BL/6J mice by myelin oligodendrocyte protein (MOG)_35–55 peptide immunization, and followed by the monitoring of clinical and pathological parameters and autoreactive T cells at different stages during the course.

Results: The dynamic changes of inflammatory infiltration, myelin loss, and astrocyte proliferation in brain and spinal cord were highly consistent with clinical severity observed in EAE course. However, the frequencies of both MOG-specific CD4⁺ and CD8⁺ T cells in secondary lymphoid organs presented different dynamic trends from the IFN-γ production by MOG-reactive T cells. Meanwhile, the IL-17 production by MOG-reactive CD4⁺ T cells was consistent with the proliferation of MOG-specific CD4⁺ T cells.

Conclusions: Both CD4⁺ and CD8⁺ T cells were most sensitive to MOG antigen stimulation for IFN-γ production during the early stage of EAE, but then rapidly lost the function despite their vigorous proliferation at the peak stage and later.

KEYWORDS:

• Autoreactive T cells
• experimental autoimmune encephalomyelitis
• multiple sclerosis
• myelin oligodendrocyte protein

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

This work was supported by the National Natural Science Foundation of China (Grant No. 81172823 and 81372448); and Science & Technology Support Program of Jiangsu Province (Grant No. BE2012739) to C. Shen. This work also was supported by Fundamental Research Funds for the Central Universities of China and the Post-graduate Research & Innovation Program of Jiangsu province (Grant No. KYCX17-0164) to X. Wan. The sponsors had no role in study design, data collection and analysis, preparation of the manuscript, or decision to submit the article for publication.

Ethics approval and consent to participate

Animal welfare and experimental procedures were performed in accordance with the Guide for the Care and Use of Laboratory Animals (Ministry of Science and Technology of China, 2006) and were approved by the Animal Ethics Committee of Southeast University.

Additional information

Notes on contributors

Chuanlai Shen

C. Shen designed and supervised the research. X. Wan, W. Pei, and Y. Zhang performed the main experiments of this study, including EAE model establishment, tissue section preparation, H&E staining, IHC analyses, and pathological observation. X. Wan analyzed and organized the whole data. K. A. Shahzad assisted in animal work, IHC analyses, and ELISPOT assay. L. Zhang and T. Xu assisted in the MHC tetramer and dimer staining, flow cytometry, and the consequent data analysis. C. Shen and X. Wan wrote the manuscript with discussions from all authors. All authors commented on the final version of the manuscript and approved the submission.