Cutting edge: CD69 interference with sphingosine-1-phosphate receptor function regulates peripheral T cell retention

LK Mackay, A Braun, BL Macleod, N Collins… - The Journal of …, 2015 - journals.aai.org
LK Mackay, A Braun, BL Macleod, N Collins, C Tebartz, S Bedoui, FR Carbone, T Gebhardt
The Journal of Immunology, 2015journals.aai.org
Tissue-resident memory T cells provide local immune protection in barrier tissues, such as
skin and mucosa. However, the molecular mechanisms controlling effector T cell retention
and subsequent memory formation in those locations are not fully understood. In this study,
we analyzed the role of CD69, an early leukocyte activation marker, in regulating effector T
cell egress from peripheral tissues. We provide evidence that CD69 surface expression by
skin-infiltrating CD8 T cells can be regulated at multiple levels, including local Ag stimulation …
Abstract
Tissue-resident memory T cells provide local immune protection in barrier tissues, such as skin and mucosa. However, the molecular mechanisms controlling effector T cell retention and subsequent memory formation in those locations are not fully understood. In this study, we analyzed the role of CD69, an early leukocyte activation marker, in regulating effector T cell egress from peripheral tissues. We provide evidence that CD69 surface expression by skin-infiltrating CD8 T cells can be regulated at multiple levels, including local Ag stimulation and signaling through type I IFNRs, and it coincides with the transcriptional downregulation of the sphingosine-1-phosphate receptor S1P 1. Importantly, we demonstrate that expression of CD69, by interfering with sphingosine-1-phosphate receptor function, is a critical determinant of prolonged T cell retention and local memory formation. Our results define an important step in the generation of long-lived adaptive immune memory at body surfaces.
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