Regulatory and T Effector Cells Have Overlapping Low to High Ranges in TCR Affinities for Self during Demyelinating Disease.
Regulatory and T Effector Cells Have Overlapping Low to High Ranges in TCR Affinities for Self during Demyelinating Disease.
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DOI：
10.4049/jimmunol.1501464
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发表时间：
2015-11-01
期刊：
影响因子：
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通讯作者：
Evavold BD
中科院分区：
文献类型：
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作者：
Hood JD;Zarnitsyna VI;Zhu C;Evavold BD
Having regulatory T cells with the same antigen specificity as the responding conventional T cells is thought to be important in maintaining peripheral tolerance. It has been demonstrated that during experimental autoimmune encephalomyelitis (EAE) there are MOG-specific Tregs that infiltrate into the central nervous system (CNS). However the affinity of naturally occurring polyclonal Tregs for any self-antigen let alone MOG has not been analyzed in the periphery or at the site of autoimmune disease. Utilizing the highly sensitive micropipette adhesion frequency assay, which allows one to determine on a single cell basis the affinity and frequency of polyclonal antigen-specific T cells directly ex vivo, we demonstrate that at peak disease MOG-specific Tregs were progressively enriched in the draining cervical lymph nodes and CNS as compared to spleen. These frequencies were greater than the frequencies measured by tetramer analysis indicative of the large fraction of lower affinity T cells that comprise the MOG specific Tconv and Treg response. Of interest, the self-reactive CD4+ Tconvs and Tregs displayed overlapping affinities for MOG in the periphery, yet in the CNS, the site of neuroinflammation, Tconvs skew towards higher affinities. The majority of the MOG-specific Tregs in the CNS possessed the methylation signature associated with thymic derived Tregs. These findings indicate that tTreg affinity range matches that of their Tconvs in the periphery and suggest a change in TCR affinity as a potential mechanism for autoimmune progression and escape from immune regulation.
