Abstract
Linker for activation of T cells (LAT) is essential for T cell activation. Mice with mutations of distinct LAT tyrosine residues (LatY136F and Lat3YF) develop lymphoproliferative disorders involving TCR alphabeta or gammadelta T cells that trigger symptoms resembling allergic inflammation. We analyzed whether these T cells share a pattern of gene expression that may account for their pathogenic properties. Both LatY136F alphabeta and Lat3YF gammadelta T cells expressed high levels of the type 1 cysteinyl leukotriene receptor (CysLT(1)). Upon binding to the 5(S)-hydroxy-6(R)-S-cysteinylglycyl-7,9-trans-11,14-cis-eicosatetraenoic acid (LTD(4)) cysteinyl leukotriene, CysLT(1) induced Ca(2+) flux and caused chemotaxis in both LatY136F alphabeta and Lat3YF gammadelta T cells. Wild-type in vitro-activated T cells, but not resting T cells, also migrated toward LTD(4) however with a lower magnitude than T cells freshly isolated from LatY136F and Lat3YF mice. These results suggest that CysLT(1) is likely involved in the recruitment of activated alphabeta and gammadelta T cells to inflamed tissues.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Adaptor Proteins, Signal Transducing / genetics
-
Animals
-
Calcium / metabolism*
-
Calcium / physiology
-
Calcium Signaling / genetics
-
Calcium Signaling / immunology*
-
Chemotaxis, Leukocyte / genetics
-
Chemotaxis, Leukocyte / immunology*
-
Intracellular Fluid / immunology
-
Intracellular Fluid / metabolism
-
Leukotriene D4 / metabolism
-
Ligands
-
Lymphocyte Activation / genetics
-
Lymphocyte Activation / immunology
-
Membrane Proteins / biosynthesis
-
Membrane Proteins / genetics
-
Membrane Proteins / physiology*
-
Mice
-
Mice, Knockout
-
Mice, Mutant Strains
-
Phenylalanine / genetics
-
Phosphoproteins / genetics
-
Receptors, Antigen, T-Cell, alpha-beta / physiology*
-
Receptors, Antigen, T-Cell, gamma-delta / physiology*
-
Receptors, Leukotriene / biosynthesis
-
Receptors, Leukotriene / genetics
-
Receptors, Leukotriene / physiology*
-
T-Lymphocyte Subsets / immunology
-
T-Lymphocyte Subsets / metabolism
-
T-Lymphocyte Subsets / pathology
-
T-Lymphocytes, Regulatory / immunology*
-
T-Lymphocytes, Regulatory / metabolism
-
T-Lymphocytes, Regulatory / pathology
-
Tyrosine / genetics
Substances
-
Adaptor Proteins, Signal Transducing
-
Lat protein, mouse
-
Ligands
-
Membrane Proteins
-
Phosphoproteins
-
Receptors, Antigen, T-Cell, alpha-beta
-
Receptors, Antigen, T-Cell, gamma-delta
-
Receptors, Leukotriene
-
Tyrosine
-
Phenylalanine
-
Leukotriene D4
-
leukotriene D4 receptor
-
Calcium