In:
The Journal of Immunology, The American Association of Immunologists, Vol. 192, No. 10 ( 2014-05-15), p. 4541-4550
Abstract:
Experimental autoimmune uveoretinitis is a model for noninfectious posterior segment intraocular inflammation in humans. Although this disease is CD4+ T cell dependent, in the persistent phase of disease CD8+ T cells accumulate. We show that these are effector memory CD8+ T cells that differ from their splenic counterparts with respect to surface expression of CD69, CD103, and Ly6C. These retinal effector memory CD8+ T cells have limited cytotoxic effector function, are impaired in their ability to proliferate in response to Ag-specific stimulation, and upregulate programmed death 1 receptor. Treatment with fingolimod (FTY720) during the late phase of disease revealed that retinal CD8+ T cells were tissue resident. Despite signs of exhaustion, these cells were functional, as their depletion resulted in an expansion of retinal CD4+ T cells and CD11b+ macrophages. These results demonstrate that, during chronic autoimmune inflammation, exhausted CD8+ T cells become established in the local tissue. They are phenotypically distinct from peripheral CD8+ T cells and provide local signals within the tissue by expression of inhibitory receptors such as programmed death 1 that limit persistent inflammation.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.1301390
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2014
detail.hit.zdb_id:
1475085-5
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