The Journal of Immunology, 2007, 178, 7501
Copyright © 2007 by The American Association of Immunologists, Inc.
Comment on "A Novel Pathway that Regulates Inflammatory Disease in the Respiratory Tract"
Chris L. Van Hove,
Tania Maes,
Guy F. Joos and
Kurt G. Tournoy
Department of Respiratory Diseases Ghent University Hospital Ghent, Belgium
In their recent article, Niu et al. (1) investigate the waning of allergic airway inflammation observed in mice repeatedly exposed to inhaled Ag. Using RAG1–/– mice, they show that the immune suppression resulting from administering inhaled Ag during both Th1- and Th2-mediated inflammation is not the consequence of actions by a regulatory T cell (Treg) population.
We recently obtained results providing further support for the notion of Treg-independent disease inhibition in mouse models using continued challenge with inhaled Ag. We found that mice with allergic airway inflammation, when continuously challenged, displayed an Ag-nonspecific and long-lasting disease inhibition (2). When we traced the evolution of the amount of CD4+CD25+foxp3+ T cells in the lung during this process, we found that both the relative and the absolute number of these cells were down-regulated in the state of immune suppression as compared with acute inflammation. This shows that the disease inhibition or "tolerance" did not critically depend on the number of Tregs, in contrast with the situation found in primary inhalational tolerance (3). Although this finding does not provide definite proof of a Treg-independent mechanism, we argue that our findings at least suggest it.
Niu et al. found the inhibitory effects to be associated with a population of TGF-
1-expressing macrophages, while we found alterations in the communication between dendritic cells and T cells. Nevertheless, no clear causal factor (meeting Koch’s postulates) was identified in both studies. Therefore, more research is needed to further characterize and identify the potent immune-suppressive mechanisms that underlie the observed waning of inflammatory disease.
References
- Niu, N., M. K. Le Goff, F. Li, M. Rahman, R. J. Homer, L. Cohn. 2007. A novel pathway that regulates inflammatory disease in the respiratory tract. J. Immunol. 178: 3846-3855. [Abstract/Free Full Text]
- Van Hove, C. L., T. Maes, G. F. Joos, K. G. Tournoy. 2007. Prolonged inhaled allergen exposure can induce persistent tolerance. Am. J. Respir. Cell Mol. Biol. 36: 573-584. [Abstract/Free Full Text]
- Ostroukhova, M., C. Seguin-Devaux, T. B. Oriss, B. Dixon-McCarthy, L. Yang, B. T. Ameredes, T. E. Corcoran, A. Ray. 2004. Tolerance induced by inhaled antigen involves CD4+ T cells expressing membrane-bound TGF- and FOXP3. J. Clin. Invest. 114: 28-38. [Medline]
