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Eur J Immunol. 2018 May;48(5):803-814. doi: 10.1002/eji.201747263. Epub 2018 Jan 19.

Hyaluronan-binding by CD44 reduces the memory potential of activated murine CD8 T cells.

Author information

1
Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, Canada.
2
Department of Pediatrics, British Columbia Children's Hospital Research Institute, University of British Columbia, Vancouver, BC, Canada.

Abstract

Expansion and death of effector CD8 T cells are regulated to limit immunopathology and cells that escape contraction go on to generate immunological memory. CD44, a receptor for the extracellular matrix component hyaluronan, is a marker of activated and memory T cells. Here, we show with a murine model that the increase in CD44 expression and hyaluronan binding induced upon CD8 T cell activation was proportional to the strength of TCR engagement, thereby identifying the most strongly activated T cells. When CD44-/- and CD44+/+ OT-I CD8 T cells were adoptively transferred into mice challenged with Listeria-OVA, there was a slight increase in the percentage of CD44+/+ cells at the effector site. However, CD44+/+ cells were out-competed by CD44-/- cells after the contraction phase in the lymphoid tissues, and the CD44-/- cells preferentially formed more memory cells. The hyaluronan-binding CD44+/+ CD8 effector T cells showed increased pAkt expression, higher glucose uptake, and were more susceptible to cell death during the contraction phase compared to non-binding CD44+/+ and CD44-/- OT-I CD8 T cells, suggesting that CD44 and its engagement with hyaluronan skews CD8 T cells toward a terminal effector differentiation state that reduces their ability to form memory cells.

KEYWORDS:

CD44; Hyaluronan; Memory CD8 T cell formation; T cell contraction

PMID:
29315518
DOI:
10.1002/eji.201747263
[Indexed for MEDLINE]
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