Emerging concepts in autoimmune encephalomyelitis beyond the CD4/T(H)1 paradigm

Area of Science:

• Neuroimmunology
• Autoimmune Diseases
• Cellular Immunology

Background:

• Multiple sclerosis (MS) and its animal model (EAE) were traditionally viewed as T helper 1 (T(H)1) cell-mediated diseases.
• Recent findings implicate T helper 17 (T(H)17) cells as potentially more pathogenic than T(H)1 cells in EAE and MS lesions.
• The role of CD8+ T cells, B cells, and innate immune cells in MS pathogenesis is increasingly recognized.

Purpose of the Study:

• To review the complex network of immune mechanisms involved in MS and EAE pathogenesis.
• To critically reevaluate the traditional CD4+/T(H)1 paradigm in light of new evidence.
• To explore the contributions of various immune cell subsets beyond T(H)1 cells.

Main Methods:

• Review of existing literature on immune cell involvement in MS and EAE.
• Analysis of data on T cell subsets (T(H)1, T(H)17, CD4+, CD8+), B cells, and innate immune cells.
• Evaluation of cellular interactions and molecular mechanisms driving neuroinflammation.

Main Results:

• T(H)17 cells are crucial for leukocyte recruitment and CNS inflammation in EAE.
• CD8+ T cells, which are more abundant than CD4+ T cells in MS lesions, can induce axonal pathology.
• B cells contribute through autoantibody production, antigen presentation, and formation of ectopic lymphoid aggregates in the CNS.
• Innate immune cells like macrophages and dendritic cells, via Toll-like receptors (TLRs), amplify inflammation.
• Regulatory immune cells, including regulatory T cells, NK cells, and NKT cells, possess suppressive functions.

Conclusions:

• The pathogenesis of MS and EAE is driven by a complex interplay of multiple immune cell types, not solely T(H)1 cells.
• The traditional CD4+/T(H)1 paradigm is insufficient to explain the full spectrum of immune involvement in MS.
• Understanding these diverse immune mechanisms is crucial for developing effective MS therapies.