Sustained exposure to bacterial antigen induces interferon-γ-dependent T cell receptorζdown-regulation and impaired T cell function

Nature Immunology 4, 957 - 964 (2003)

Speaker: 曾昭穎                    Time: 15:00~16:00 1/7/2004

Commentator: 謝奇璋 醫師          Place: Room 601

Abstract:

   The T-cell antigen receptor ζchain plays an important role in coupling antigen recognition to several intracellular signal-transduction pathways. In previous studies, decreased ζchain expression was found in peripheral blood lymphocytes of patients with head and neck cancer. In other diseases like autoimmune diseases and tumors , people also observed the down-regulation of ζchain. The above data implied that TCR-ζmight be useful as an indicator of T-cell function. In addition, repeated bacterial challenge in a subcutaneous chamber model results in enlarged TNF-α and IFN-γ , and oppression of IL-10. In this article, the authors established an in vivo experimental system that they sustained treatment of Porphyromonas gingivalis to induce a T_H-1 dominant inflammatory immune response in mice, to account forζchain down-regulation in cancer and autoimmune and infectious diseases. In their model, onlyζchain is being down-regulated whileCD3ε, one of  the TCR subunits, is unaffected. However, ζchain down-regulation is mainly caused by lysosomal degradation. They also noticed that when exposure of the mice to P. gingivalis is stopped, ζchain levels and T cell function gradually returned to normal. The results also showed that a mixture of T_H1-T_H2 immune responses is elicited. All of the results support their conclusion that a T_H1 immune response is required for the induction of ζdown-regulation, and that the presence of a T_H2 immune response has no effect on ζchain expression. Briefly, these studies demonstrated that down - regulation of ζchain could be a normal mechanism for controlling an excessive and potentially hazardous immune response.

References:

1.     Houri-Haddad Y. et al. Interferon-gamma Deficiency Attenuates Local P. gingivalis-induced Inflammation. J Dent Res. 2002 81(6): 395-398,

2.     Houri-Haddad  Y. et  al.  Repeat bacterial challenge in a subcutaneous chamber model results in augmented TNF-α and IFN-γ response, and suppression of IL-10. Immunology. 2000 Feb; 99(2): 215-20.