CD44 Regulates Survival and Memory Development in Th1 Cells

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 expre...

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Bibliographic Details
Published in:Immunity (Cambridge, Mass.) Mass.), 2010-01, Vol.32 (1), p.104-115
Main Authors: Baaten, Bas J.G., Li, Cheng-Rui, Deiro, Mia F., Lin, Melissa M., Linton, Phyllis J., Bradley, Linda M.
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Apoptosis - immunology
Cell adhesion & migration
Cell division
CELLIMMUNO
Cytokines
Flow cytometry
Hyaluronan Receptors - immunology
Hyaluronan Receptors - metabolism
Immunoblotting
Immunologic Memory - immunology
Kinases
Lymphocyte Activation - immunology
Lymphocytes
Mice
Mice, Inbred C57BL
Mice, Knockout
MOLIMMUNO
Orthomyxoviridae Infections
Reverse Transcriptase Polymerase Chain Reaction
Rodents
Signal Transduction - immunology
T cell receptors
T-Lymphocyte Subsets - immunology
T-Lymphocyte Subsets - metabolism
Th1 Cells - immunology
Th1 Cells - metabolism
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Summary: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. ► Without CD44, Th1 cells fail to generate memory to influenza virus infection ► CD44 controls the survival of CD4 + Th1 cells, but not Th2, Th17, nor CD8 + T cells ► Ligation of CD44 with an agonist antibody elicits PI3 kinase-Akt survival signal
ISSN:1074-7613
1097-4180
DOI:10.1016/j.immuni.2009.10.011