Induction of T helper type 2 immunity by a point mutation in the LAT adaptor

The transmembrane protein LAT (tinker 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 (T-H) cells that chronically produced type 2 cytokines in large amounts. This exaggerated T(H)2 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 T-H cells.