Up-regulation of the phosphoinositide 3-kinase pathway in human lamina propria T lymphocytes.
Human intestinal lamina propria T lymphocytes (LPT), when investigated ex vivo, exhibit functional properties profoundly different from those of peripheral blood T lymphocytes (PBT). One prominent feature represents their enhanced sensitivity to CD2 stimulation when compared to PBT. Given that LPT are hyporesponsive to T cell receptor (TCR)/CD3 stimulation, an alternative activation mode, as mimicked by CD2 triggering in vitro, may be functional in mucosal inflammation in vivo. This study provides insight into signalling events associated with the high CD2 responsiveness of LPT. When compared to PBT, LPT show an increased activation of the phosphoinositide 3/protein kinase B/glycogen synthase kinase 3beta (PI3-kinase/AKT/GSK-3beta) pathway in response to CD2 stimulation. Evidence is provided that up-regulation of this pathway contributes to the enhanced CD2-induced cytokine production in LPT. Given the importance of TCR-independent stimulation for the initiation of intestinal immune responses analysis of signalling pathways induced by 'co-stimulatory' receptors may provide valuable information for therapeutic drug design.
Braunstein
J
J
Institute for Immunology, University of Heidelberg, Heidelberg, Germany.
Autschbach
F
F
Giese
T
T
Lasitschka
F
F
Heidtmann
A
A
Sido
B
B
Funke
B
B
Reiser
C
C
Schröder
A J
AJ
Nebl
G
G
Samstag
Y
Y
Meuer
S C
SC
D018801:CD2 Antigens / Q000276:immunology; D023201:CD40 Ligand / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D018928:Immunity, Mucosal; D007376:Interleukin-2 / Q000096:biosynthesis; D007413:Intestinal Mucosa / Q000276:immunology*; D017493:Leukocyte Common Antigens / Q000032:analysis; D009092:Mucous Membrane / Q000276:immunology; D019869:Phosphatidylinositol 3-Kinases / Q000096:biosynthesis* / Q000235:genetics; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D015854:Up-Regulation / Q000276:immunology*
D018801:CD2 Antigens; D016207:Cytokines; D007376:Interleukin-2; D023201:CD40 Ligand; D019869:Phosphatidylinositol 3-Kinases; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; D017493:Leukocyte Common Antigens