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Defect in TCR-CD3zeta signaling mediates T cell hypo-responsiveness in mesenteric lymph node

Authors
 Hwa-Jung Yi  ;  Choong-Gu Lee  ;  Ho-Keun Kwon  ;  Jae-Seon So  ;  Anupama Sahoo  ;  Ji-Sun Hwang  ;  Arijita Jash  ;  Ki-Chul Hwang  ;  Sin-Hyeog Im 
Citation
 MOLECULAR IMMUNOLOGY, Vol.45(14) : 3748-3755, 2008 
Journal Title
 MOLECULAR IMMUNOLOGY 
ISSN
 0161-5890 
Issue Date
2008
MeSH
Animals ; CD3 Complex/immunology* ; Lymph Nodes/immunology* ; Mesentery/immunology ; Mice ; Mice, Inbred BALB C ; Receptors, Antigen, T-Cell/immunology* ; Signal Transduction/immunology* ; T-Lymphocytes/immunology*
Keywords
Rodent ; Mucosa ; Mesenteric lymph node ; T cells ; T cell receptors ; CD3ζ ; Tolerance ; Anergy ; GALT
Abstract
Mesenteric lymph node (MLN) in gut-associated lymphoid tissue plays obligatory roles in the induction of oral tolerance and ignorance to commensals. However, little is known about its immunological characteristics. In this study, we investigated the hypo-responsiveness of MLN CD4(+) T cells, comparing them with spleen CD4(+) T cells. MLN CD4(+) T cells were hypo-proliferative and expressed low levels of Th1-type cytokines in response to antigen or CD3/T cell receptor (TCR) stimulation. The hypo-responsiveness of MLN CD4(+) T cells is linked neither with changes in the regulatory T cell population (CD4(+)CD25(+), CD4(+)Foxp3(+)) nor the apoptotic population. Rather, MLN CD4(+) T cells showed deformity of T cell:APC conjugation and reduced expression of TCR signaling molecules such as CD3zeta, PLC-gamma1, PKC-theta, Zap70, with reduced phosphorylation of immunoreceptor tyrosine-based activation motifs (ITAMs). Among the alterations in TCR signaling molecules, defective CD3zeta expression is the most evident, and reversal of the anergic state by CD3/CD28 costimulation restored CD3zeta expression levels. Collectively, we suggest that reduced CD3zeta expression and defects in TCR signaling mediate the anergy state of MLN CD4(+) T cells, which play a critical role in maintenance of mucosal tolerance in gut-associated lymphoid tissue
Full Text
http://www.sciencedirect.com/science/article/pii/S0161589008002253
DOI
10.1016/j.molimm.2008.05.025
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
Yonsei Authors
Hwang, Ki Chul(황기철)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/106568
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