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.
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/