Myelin protein expression in lymphoid tissues: implications for peripheral tolerance

Area of Science:

• Neuroimmunology
• Autoimmunity
• T cell immunology

Background:

• Chronic relapsing experimental autoimmune encephalomyelitis (EAE) involves T lymphocytes targeting myelin protein epitopes.
• Epitope spreading, where T cells respond to unique epitopes, is typically observed during EAE relapses.
• The location of T cell stimulation during EAE relapses, especially with myelin proteins sequestered by the blood-brain barrier, remains unclear.

Purpose of the Study:

• To investigate the site of T lymphocyte stimulation during the relapsing phase of EAE.
• To test the hypothesis that epitope spreading occurs within lymphoid tissues rather than the central nervous system (CNS).

Main Methods:

• Analysis of myelin basic protein (MBP) and proteolipid protein (PLP) expression at RNA and protein levels in lymphoid tissues (lymph node, thymus, spleen) of EAE mice.
• Detection of myelin protein expression within lymphocytes and macrophages.
• Assessment of T lymphocyte line recognition of endogenous myelin proteins from lymphoid-derived cells.

Main Results:

• Myelin basic protein (MBP) and proteolipid protein (PLP) are expressed in the lymph node, thymus, and spleen of mice with relapsing EAE.
• This expression occurs within T lymphocytes, B lymphocytes, and macrophages.
• T lymphocyte lines recognize endogenous myelin proteins presented by cells from lymphoid tissues.

Conclusions:

• Immunologically relevant myelin proteins are endogenously produced and presented within lymphoid tissues during EAE.
• Epitope spreading in EAE likely occurs within lymphoid tissues, not the CNS.
• This lymphoid-based activation explains T cell entry into the CNS and lesion formation during relapses.