Increase in Th17 and T-reg lymphocytes and decrease of IL22 correlate with the recovery phase of acute EAE in rat

Area of Science:

• Neuroimmunology
• Immunology
• Animal Models of Disease

Background:

• Experimental autoimmune encephalomyelitis (EAE) is a key animal model for studying multiple sclerosis (MS).
• EAE in Lewis rats typically presents as an acute, monophasic disease with spontaneous recovery and tolerance.
• Understanding lymphocyte and cytokine dynamics is crucial for deciphering EAE pathogenesis and recovery mechanisms.

Purpose of the Study:

• To comprehensively analyze the dynamic changes in lymphocyte populations and cytokine profiles during the acute EAE model in Lewis rats.
• To correlate these immunological changes with distinct disease phases: induction, peak, recovery, and post-recovery.
• To compare the observed patterns with those in chronic or relapsing-remitting EAE mouse models.

Main Methods:

• Induction of EAE in Lewis rats using myelin basic protein (MBP).
• Sacrifice of rats based on clinical scores to capture specific disease phases.
• Analysis of spinal cord tissue using flow cytometry, immunohistochemistry, and ELISA to quantify T-lymphocyte subsets (CD3+, CD4+, Th1, Th17, T-reg) and cytokines (IL-10, IL-17, IL-21, IL-22).

Main Results:

• During induction and peak phases, CD3+ and CD4+ T-cells, predominantly Th1 phenotype, increased with symptom severity.
• Unexpectedly, during the recovery phase, CD3+ and CD4+ cell numbers remained stable despite decreasing clinical signs.
• Recovery was associated with a decrease in Th1 cells and a significant increase in Th17 and T-regulatory (T-reg) cells, alongside specific cytokine profile changes (decreased IL-21, stable IL-10/IL-17, high IL-22 during peak, decreasing during recovery).

Conclusions:

• Acute EAE in Lewis rats exhibits a unique pattern of lymphocyte infiltration and cytokine secretion during recovery, differing from chronic mouse models.
• The increase in Th17 and T-reg cells during the recovery phase suggests a critical role in resolving inflammation and promoting recovery in this specific EAE model.
• These findings highlight distinct immunological mechanisms underlying acute monophasic EAE compared to chronic or relapsing-remitting forms of the disease.