Induction of T helper type 2 immunity by a point mutation in the LAT adaptor.
The transmembrane protein LAT (linker for activation of T cells) couples the T cell receptor (TCR) to downstream signaling effectors. Mice homozygous for a mutation of a single LAT tyrosine residue showed impeded T cell development. However, later they accumulated polyclonal helper T (TH) cells that chronically produced type 2 cytokines in large amounts. This exaggerated TH2 differentiation caused tissue eosinophilia and massive maturation of plasma cells secreting to immunoglobulins of the E and G1 isotypes. This paradoxical phenotype establishes an unanticipated inhibitory function for LAT that is critical for the differentiation and homeostasis of TH cells.
Aguado
Enrique
E
Centre d'Immunologie de Marseille-Luminy, INSERM- and CNRS-Université de la Méditerranée, Parc Scientifique de Luminy, 13288 Marseille Cedex 9, France.
Richelme
Sylvie
S
Nuñez-Cruz
Selene
S
Miazek
Arkadiusz
A
Mura
Anne-Marie
AM
Richelme
Mireille
M
Guo
Xiao-Jun
XJ
Sainty
Danielle
D
He
Hai-Tao
HT
Malissen
Bernard
B
Malissen
Marie
M
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000502:physiology; D018956:CD5 Antigens / Q000032:analysis / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000502:physiology; D002352:Carrier Proteins / Q000235:genetics* / Q000502:physiology*; D002453:Cell Cycle; D002454:Cell Differentiation; D004802:Eosinophilia; D004804:Eosinophils / Q000502:physiology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D007378:Interleukins / Q000235:genetics / Q000378:metabolism; D007958:Leukocyte Count; D008213:Lymphocyte Activation; D008221:Lymphoid Tissue / Q000166:cytology / Q000276:immunology; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D010641:Phenotype; D010750:Phosphoproteins / Q000235:genetics* / Q000502:physiology*; D017354:Point Mutation; D011948:Receptors, Antigen, T-Cell / Q000032:analysis; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000502:physiology; D018418:Th2 Cells / Q000276:immunology* / Q000502:physiology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology
D048868:Adaptor Proteins, Signal Transducing; D018956:CD5 Antigens; D002352:Carrier Proteins; D000949:Histocompatibility Antigens Class II; D007074:Immunoglobulin G; D007378:Interleukins; C491734:Lat protein, mouse; D008565:Membrane Proteins; D010750:Phosphoproteins; D011948:Receptors, Antigen, T-Cell; D007073:Immunoglobulin E; D007371:Interferon-gamma