title: Hyaluronan binding identifies the most proliferative activated and memory T cells.
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(+) CD44(hi)). 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.
authors.affiliation: Department of Microbiology and Immunology, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Nina
authors.initials: N
authors.lastname: Maeshima
authors.forename: Grace F T
authors.initials: GF
authors.lastname: Poon
authors.forename: Manisha
authors.initials: M
authors.lastname: Dosanjh
authors.forename: Jackie
authors.initials: J
authors.lastname: Felberg
authors.forename: Sally S M
authors.initials: SS
authors.lastname: Lee
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Cross
authors.forename: Darlene
authors.initials: D
authors.lastname: Birkenhead
authors.forename: Pauline
authors.initials: P
authors.lastname: Johnson
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D049109:Cell Proliferation; D006706:Homeostasis; D006820:Hyaluronic Acid / Q000276:immunology*; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D006820:Hyaluronic Acid