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- Title
Hyaluronan‐binding by CD44 reduces the memory potential of activated murine CD8 T cells.
- Authors
Lee‐Sayer, Sally S. M.; Maeshima, Nina; Dougan, Meghan N.; Dahiya, Anita; Arif, Arif A.; Dosanjh, Manisha; Maxwell, Christopher A.; Johnson, Pauline
- Abstract
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.
- Publication
European Journal of Immunology, 2018, Vol 48, Issue 5, p803
- ISSN
0014-2980
- Publication type
Article
- DOI
10.1002/eji.201747263