title: CD44 regulates survival and memory development in Th1 cells.
abstract: Optimal immunity to microorganisms depends upon the regulated death of clonally expanded effector cells and the survival of a cohort of cells that become memory cells. After activation of naive T cells, CD44, a widely expressed receptor for extracellular matrix components, is upregulated. High expression of CD44 remains on memory cells and despite its wide usage as a "memory marker," its function is unknown. Here we report that CD44 was essential for the generation of memory T helper 1 (Th1) cells by promoting effector cell survival. This dependency was not found in Th2, Th17, or CD8(+) T cells despite similar expression of CD44 and the absence of splice variants in all subsets. CD44 limited Fas-mediated death in Th1 cells and its ligation engaged the phosphoinositide 3-kinase-Akt kinase signaling pathway that regulates cell survival. The difference in CD44-regulated apoptosis resistance in T cell subpopulations has important implications in a broad spectrum of diseases.
authors.affiliation: Infectious and Inflammatory Diseases Center, Burnham Institute for Medical Research, La Jolla, CA 92037, USA.
authors.forename: Bas J G
authors.initials: BJ
authors.lastname: Baaten
authors.forename: Cheng-Rui
authors.initials: CR
authors.lastname: Li
authors.forename: Mia F
authors.initials: MF
authors.lastname: Deiro
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Lin
authors.forename: Phyllis J
authors.initials: PJ
authors.lastname: Linton
authors.forename: Linda M
authors.initials: LM
authors.lastname: Bradley
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology; D018960:Hyaluronan Receptors / Q000276:immunology* / Q000378:metabolism; D015151:Immunoblotting; D007156:Immunologic Memory / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009976:Orthomyxoviridae Infections; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism
chemical_list: D018960:Hyaluronan Receptors