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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.

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


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.


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

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