T cell, Ig domain, mucin domain-2 gene-deficient mice reveal a novel mechanism for the regulation of Th2 immune responses and airway inflammation.
The development of asthma and other atopic diseases is influenced by cytokines produced by Th2 effector T cells. How effector T cell responses are regulated once these cell populations are established remains unclear. The recently described T cell and airway phenotype regulator locus, containing the T cell, Ig domain, mucin domain (TIM) genes, is genetically associated with Th2 cytokine production and Th2-dependent immune responses. In this study, we report the phenotype of the TIM-2 gene-deficient mouse, and demonstrate exacerbated lung inflammation in an airway atopic response model. Immune responses in the TIM-2-deficient mouse reveal disregulated expression of Th2 cytokines, and adoptive transfer experiments show that the T cell compartment is responsible for the heightened inflammatory phenotype. These studies show that TIM-2 is a novel and critical regulator of effector T cell activity.
Rennert
Paul D
PD
Biogen-Idec, 12 Cambridge Center, Cambridge, MA 01746, USA. paul.rennert@biogenidec.com
Ichimura
Takaharu
T
Sizing
Irene D
ID
Bailly
Veronique
V
Li
Zhifang
Z
Rennard
Rachel
R
McCoon
Patricia
P
Pablo
Lourdes
L
Miklasz
Steven
S
Tarilonte
Leticia
L
Bonventre
Joseph V
JV
D000818:Animals; D001249:Asthma / Q000276:immunology; D002454:Cell Differentiation; D004195:Disease Models, Animal; D005434:Flow Cytometry; D007249:Inflammation / Q000276:immunology*; D008168:Lung / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D010047:Ovalbumin / Q000276:immunology; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology*
D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins; D010047:Ovalbumin