| First Author | Lee-Sayer SSM | Year | 2018 |
| Journal | Eur J Immunol | Volume | 48 |
| Issue | 5 | Pages | 803-814 |
| PubMed ID | 29315518 | Mgi Jnum | J:262776 |
| Mgi Id | MGI:6160708 | Doi | 10.1002/eji.201747263 |
| Citation | Lee-Sayer SSM, et al. (2018) Hyaluronan-binding by CD44 reduces the memory potential of activated murine CD8 T cells. Eur J Immunol 48(5):803-814 |
| abstractText | 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. |
