Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Adaptor Proteins, Signal Transducing*
-
Animals
-
B-Lymphocytes / immunology
-
B-Lymphocytes / physiology
-
CD4-Positive T-Lymphocytes / immunology
-
CD4-Positive T-Lymphocytes / physiology
-
CD5 Antigens / analysis
-
CD5 Antigens / metabolism
-
CD8-Positive T-Lymphocytes / immunology
-
CD8-Positive T-Lymphocytes / physiology
-
Carrier Proteins / genetics*
-
Carrier Proteins / physiology*
-
Cell Cycle
-
Cell Differentiation
-
Eosinophilia
-
Eosinophils / physiology
-
Histocompatibility Antigens Class II / immunology
-
Immunoglobulin E / blood
-
Immunoglobulin G / blood
-
Interferon-gamma / genetics
-
Interferon-gamma / metabolism
-
Interleukins / genetics
-
Interleukins / metabolism
-
Leukocyte Count
-
Lymphocyte Activation
-
Lymphoid Tissue / cytology
-
Lymphoid Tissue / immunology
-
Membrane Proteins*
-
Mice
-
Mice, Inbred BALB C
-
Phenotype
-
Phosphoproteins / genetics*
-
Phosphoproteins / physiology*
-
Point Mutation*
-
Receptors, Antigen, T-Cell / analysis
-
Signal Transduction
-
T-Lymphocyte Subsets / immunology
-
T-Lymphocyte Subsets / physiology
-
Th2 Cells / immunology*
-
Th2 Cells / physiology
-
Thymus Gland / cytology
-
Thymus Gland / immunology
Substances
-
Adaptor Proteins, Signal Transducing
-
CD5 Antigens
-
Carrier Proteins
-
Histocompatibility Antigens Class II
-
Immunoglobulin G
-
Interleukins
-
Lat protein, mouse
-
Membrane Proteins
-
Phosphoproteins
-
Receptors, Antigen, T-Cell
-
Immunoglobulin E
-
Interferon-gamma