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.
Original language | English |
---|---|
Pages (from-to) | 4541-4550 |
Number of pages | 10 |
Journal | Journal of Immunology |
Volume | 192 |
Issue number | 10 |
DOIs | |
Publication status | Published - 15 May 2014 |
Keywords
- Uveitis
- CD8-Positive T-Lymphocytes
- Autoimmunity
Fingerprint
Dive into the research topics of 'Tissue-Resident Exhausted Effector Memory CD8+ T Cells Accumulate in the Retina during Chronic Experimental Autoimmune Uveoretinitis'. Together they form a unique fingerprint.Profiles
-
Dr Lindsay B Nicholson
- School of Cellular and Molecular Medicine - Reader in Research
- Infection and Immunity
- Ophthalmology
Person: Academic , Member, Group lead