In healthy primates, circulating autoreactive T cells mediate autoimmune disease

Area of Science:

• Neuroimmunology
• Autoimmunity
• Demyelinating Diseases

Background:

• T cell responses to myelin basic protein (MBP) are implicated in multiple sclerosis (MS) pathogenesis.
• Investigating the role of circulating MBP-reactive T cells in initiating central nervous system (CNS) inflammation is crucial.

Purpose of the Study:

• To determine if MBP-reactive T cells from peripheral circulation can induce CNS inflammatory disease.
• To utilize the unique chimeric nature of Callithrix jacchus (C. jacchus) marmosets for adoptive T cell transfer studies.

Main Methods:

• Isolation of MBP-reactive T cell clones from healthy, unimmunized C. jacchus marmosets.
• Adoptive transfer of these T cell clones between C. jacchus chimeric siblings.
• Observation and analysis of induced CNS inflammation and demyelination.

Main Results:

• MBP-reactive T cell clones efficiently transferred CNS inflammatory disease between C. jacchus chimeric sets.
• Adoptive transfer did not induce the characteristic demyelination seen in experimental allergic encephalomyelitis (EAE).
• Encephalitogenic T cell clones exhibited diverse recognition of MBP epitopes, unlike restricted responses in some rodents.

Conclusions:

• This study provides the first direct evidence that naturally occurring, circulating T cells targeting a CNS antigen can mediate inflammatory autoimmune disease.
• MBP-reactive T cells are capable of inducing CNS inflammation, supporting their role in autoimmune demyelinating conditions.
• The diverse epitope recognition in C. jacchus suggests a broader T cell response against MBP in this species.