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Science 296 (5575): 2036-2040

Copyright © 2002 by the American Association for the Advancement of Science

Induction of T Helper Type 2 Immunity by a Point Mutation in the LAT Adaptor

Enrique Aguado,1 Sylvie Richelme,1 Selene Nuñez-Cruz,1 Arkadiusz Miazek,1 Anne-Marie Mura,1 Mireille Richelme,1 Xiao-Jun Guo,1* Danielle Sainty,2 Hai-Tao He,1 Bernard Malissen,1dagger Marie Malissen1

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.

1 Centre d'Immunologie de Marseille-Luminy, INSERM- and CNRS-Université de la Méditerranée, Parc Scientifique de Luminy, 13288 Marseille Cedex 9, France.
2 Department of Biology, Institut Paoli-Calmettes, 232 Boulevard Sainte Marguerite, 13009 Marseille, France.
*   On leave from Institut Méditerranéen de Recherche en Nutrition, UMR-INRA, Marseille, France.

dagger    To whom correspondence should be addressed. E-mail: bernardm{at}ciml.univ-mrs.fr



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