Hyaluronan binding identifies the most proliferative activated and memory T cells |
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Authors: | Maeshima Nina Poon Grace F T Dosanjh Manisha Felberg Jackie Lee Sally S M Cross Jennifer L Birkenhead Darlene Johnson Pauline |
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Institution: | Department of Microbiology and Immunology, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada. |
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Abstract: | CD44 is expressed on T cells where its ability to bind hyaluronan is tightly regulated. Here, we investigated when T cells bind hyaluronan during an immune response. We found that naïve, murine T cells do not bind fluoresceinated hyaluronan but are induced to bind upon antigen‐induced T‐cell activation in vitro and in vivo. Hyaluronan binding occurred on proliferating T cells and the percentage of hyaluronan‐binding cells correlated with the strength of the activation stimulus. A small percentage of hyaluronan‐binding cells persisted after in vitro activation and had a memory phenotype (CD122+CD44hi). This hyaluronan‐binding population increased after culture with IL‐7 or IL‐15 and proliferated more rapidly than nonbinding cells. In vivo, approximately 20–30% of antigen‐specific OT‐I CD8+ memory T cells in the spleen and BM bound hyaluronan. Hyaluronan binding identified memory cells that proliferated faster in IL‐7 and IL‐15, and enriched for CD62L+ central memory cells. In vivo homeostatic proliferation induced hyaluronan binding on a small percentage of the most rapidly dividing cells after several cell divisions. This study demonstrates that hyaluronan binding is induced upon antigen‐induced T‐cell activation and occurs on a percentage of the most proliferative activated and memory T cells. |
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Keywords: | CD44 Hyaluronan T‐cell activation T‐cell memory T‐cell proliferation |
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