Journal article
IL-15 regulates memory CD8+ T cell O-glycan synthesis and affects trafficking
The Journal of clinical investigation, Vol.124(3), pp.1013-1026
03/03/2014
DOI: 10.1172/JCI72039
PMCID: PMC3934158
PMID: 24509081
Abstract
Memory and naive CD8
+
T cells exhibit distinct trafficking patterns. Specifically, memory but not naive CD8
+
T cells are recruited to inflamed tissues in an antigen-independent manner. However, the molecular mechanisms that regulate memory CD8
+
T cell trafficking are largely unknown. Here, using murine models of infection and T cell transfer, we found that memory but not naive CD8
+
T cells dynamically regulate expression of core 2 O-glycans, which interact with P- and E-selectins to modulate trafficking to inflamed tissues. Following infection, antigen-specific effector CD8
+
T cells strongly expressed core 2 O-glycans, but this glycosylation pattern was lost by most memory CD8
+
T cells. After unrelated infection or inflammatory challenge, memory CD8
+
T cells synthesized core 2 O-glycans independently of antigen restimulation. The presence of core 2 O-glycans subsequently directed these cells to inflamed tissue. Memory and naive CD8
+
T cells exhibited the opposite pattern of epigenetic modifications at the
Gcnt1
locus, which encodes the enzyme that initiates core 2 O-glycan synthesis. The open chromatin configuration in memory CD8
+
T cells permitted de novo generation of core 2 O-glycans in a TCR-independent, but IL-15–dependent, manner. Thus, IL-15 stimulation promotes antigen-experienced memory CD8
+
T cells to generate core 2 O-glycans, which subsequently localize them to inflamed tissues. These findings suggest that CD8
+
memory T cell trafficking potentially can be manipulated to improve host defense and immunotherapy.
Details
- Title: Subtitle
- IL-15 regulates memory CD8+ T cell O-glycan synthesis and affects trafficking
- Creators
- Jeffrey C Nolz - Department of MicrobiologyJohn T Harty - Department of Microbiology
- Resource Type
- Journal article
- Publication Details
- The Journal of clinical investigation, Vol.124(3), pp.1013-1026
- Publisher
- American Society for Clinical Investigation
- DOI
- 10.1172/JCI72039
- PMID
- 24509081
- PMCID
- PMC3934158
- ISSN
- 0021-9738
- eISSN
- 1558-8238
- Language
- English
- Date published
- 03/03/2014
- Academic Unit
- Pathology
- Record Identifier
- 9984047681102771
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