The T-cell antigen receptor zeta (ζ) chain contains signal-transducing motifs, and its downregulation has been linked with impaired in vitro T-cell function in cancer and autoimmune and infectious diseases. However, the exact molecular mechanisms involved are unknown. In the September 21 Nature Immunology, Noemí Bronstein-Sitton and colleagues at the Hebrew University-Hadassah Medical School show that reduced ζ expression is the normal outcome of an excessive and potentially hazardous immune response (Nature Immunology, DOI:10.1038/ni975, September 21, 2003).

Bronstein-Sitton et al. used an in vivo system that mimics chronic infections by exposing healthy mice to heat-killed Porphyromonas gingivalis. They observed that sustained exposure of mice to bacterial antigens was sufficient to induce T-cell antigen receptor ζ chain downregulation and impair T-cell function. In addition, the authors showed that downregulation of ζ correlated with an impaired in vivo T-cell–mediated immune response—a phenomenon that required interferon γand a TH1-dependent immune...

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