TY - JOUR
T1 - Memory phenotype CD8+ T cells with innate function selectively develop in the absence of active Itk
AU - Hu, Jianfang
AU - Sahu, Nisebita
AU - Walsh, Elizabeth
AU - August, Avery
PY - 2007/10
Y1 - 2007/10
N2 - T cells with a memory-like phenotype and possessing innate immune function have been previously identified as CD8+CD44hi cells. These cells rapidly secrete IFN-γ upon stimulation with IL-12/IL-18 and are involved in innate responses to infection with Listeria monocytogenes. The signals regulating these cells are unclear. The Tec kinase Itk regulates T cell activation and we report here that a majority of the CD8+ T cells in Itk null mice have a phenotype of CD44hi similar to memory-like innate T cells. These cells are observed in mice carrying an Itk mutant lacking the kinase domain, indicating that active Tec kinase signaling suppresses their presence. These cells carry preformed message for and are able to rapidly produce IFN-γ upon stimulation in vitro with IL-12/IL-18, and endow Itk null mice the ability to effectively respond to infection with L. monocytogenes or exposure to lipopolysaccharides by secretion of IFN-γ. Transfer of these cells rescues the ability of IFN-γ null mice to reduce bacterial burden following L. monocytogenes infection, indicating that these cells are functional CD8+CD44hi T cells previously detected in vivo. These results indicate that active signals from Tec kinases regulate the development of memory-like CD8+ T cells with innate function.
AB - T cells with a memory-like phenotype and possessing innate immune function have been previously identified as CD8+CD44hi cells. These cells rapidly secrete IFN-γ upon stimulation with IL-12/IL-18 and are involved in innate responses to infection with Listeria monocytogenes. The signals regulating these cells are unclear. The Tec kinase Itk regulates T cell activation and we report here that a majority of the CD8+ T cells in Itk null mice have a phenotype of CD44hi similar to memory-like innate T cells. These cells are observed in mice carrying an Itk mutant lacking the kinase domain, indicating that active Tec kinase signaling suppresses their presence. These cells carry preformed message for and are able to rapidly produce IFN-γ upon stimulation in vitro with IL-12/IL-18, and endow Itk null mice the ability to effectively respond to infection with L. monocytogenes or exposure to lipopolysaccharides by secretion of IFN-γ. Transfer of these cells rescues the ability of IFN-γ null mice to reduce bacterial burden following L. monocytogenes infection, indicating that these cells are functional CD8+CD44hi T cells previously detected in vivo. These results indicate that active signals from Tec kinases regulate the development of memory-like CD8+ T cells with innate function.
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U2 - 10.1002/eji.200737311
DO - 10.1002/eji.200737311
M3 - Article
C2 - 17724684
AN - SCOPUS:35348835445
SN - 0014-2980
VL - 37
SP - 2892
EP - 2899
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 10
ER -