Th2 Lymphoproliferative Disorder of Lat Mutant Mice Unfolds Independently of TCR-MHC Engagement and Is Insensitive to the Action of Foxp3 Regulatory T Cells

نویسندگان

  • Bernard Malissen
  • James P. DiSanto
  • Hans Acha-Orbea
  • Sylvie Richelme
  • Pierre Perrin
  • Stéphane Chevrier
  • Ying Wang
  • Adrien Kissenpfennig
  • Michael Mingueneau
  • Céline Genton
  • Bruno Lucas
  • Marie Malissen
چکیده

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Th2 lymphoproliferative disorder of LatY136F mutant mice unfolds independently of TCR-MHC engagement and is insensitive to the action of Foxp3+ regulatory T cells.

Mutant mice where tyrosine 136 of linker for activation of T cells (LAT) was replaced with a phenylalanine (Lat(Y136F) mice) develop a fast-onset lymphoproliferative disorder involving polyclonal CD4 T cells that produce massive amounts of Th2 cytokines and trigger severe inflammation and autoantibodies. We analyzed whether the Lat(Y136F) pathology constitutes a bona fide autoimmune disorder de...

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Mutant mice in which tyrosine 136 of linker for activation of T cells (LAT) was replaced with a phenylalanine (Lat(Y136F) mice) develop a lymphoproliferative disorder involving polyclonal CD4 effector T cells that produce massive amounts of IL-4 and trigger severe Th2 inflammation. Naive CD4 T cells can themselves produce IL-4 and thereby initiate a self-reinforcing positive regulatory loop tha...

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Objective(s): Th2 response is related to the aetiology of asthma, but the underlying mechanism is unclear. To address this point, the effect of nebulized inhalation of inactivated Mycobacterium phlei on modulation of asthmatic  airway  inflammation was investigated. Materials and Methods: 24 male BALB/c mice were randomly divided into three groups: control group (Group A), asthma model group (G...

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LAT-mediated signaling in CD4+CD25+ regulatory T cell development

Engagement of the T cell receptor for antigen (TCR) induces formation of signaling complexes mediated through the transmembrane adaptor protein, the linker for activation of T cells (LAT). LAT plays an important role in T cell development, activation, and homeostasis. A knock-in mutation at Tyr136, which is the phospholipase C (PLC)-gamma1-binding site in LAT, leads to a severe autoimmune disea...

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تاریخ انتشار 2008