Chronic infections and excessive immune responses cause reduced T-cell antigen æ expression By Tudor Toma
The T-cell antigen receptor zeta (æ) 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 æ 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 æ chain downregulation and impair T-cell function. In addition, the authors showed that downregulation of æ correlated with an impaired in vivo T-cell–mediated immune response—a phenomenon that required interferon ãand a TH1-dependent immune response.
"We propose that æd own-regulation could be one of the mechanisms that 'shuts off' an inappropriately extreme immune response, thus maintaining balance in the immune system," conclude the authors.
Subscribe to the World's Most Popular Newsletter (it's free!)
Links for this article:
E.W. Shores P.E. Love, "TCR zeta chain in T cell development and selection," Current Opinion in Immunology, 9:380-389, June 1997.
N. Bronstein-Sitton et al., "Sustained exposure to bacterial antigen induces interferon-ã -dependent T cell receptor æ down-regulation and impaired T cell function," Nature Immunology, DOI:10.1038/ni975, September 21, 2003. http://www.nature.com/ni/
Hebrew University-Hadassah Medical School http://www.md.huji.ac.il/