This Article Full Text Full Text (PDF) All Versions of this Article: 200305-634OCv1 168/11/1324    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cui, Z.-H. Articles by Gelfand, E. W. Search for Related Content PubMed PubMed Citation Articles by Cui, Z.-H. Articles by Gelfand, E. W.

Reversal of Allergic Airway Hyperreactivity after Long-term Allergen Challenge Depends on T Cells

Program in Cell Biology, Department of Pediatrics, and Department of Immunology, National Jewish Medical and Research Center, Denver, Colorado

Correspondence and requests for reprints should be addressed to Erwin W. Gelfand, M.D., National Jewish Medical and Research Center, 1400 Jackson Street, Denver, CO 80206. E-mail: gelfande{at}njc.org

Long-term allergen exposure can attenuate inflammation and revert airway hyperreactivity to normal responsiveness. A model of such reversal was established in which airway hyperreactivity and inflammation in ovalbumin-sensitized and challenged mice were decreased after multiple daily airway challenges. This change in responsiveness and inflammation was associated with a transition from a helper T cell Type 2 to a helper T cell Type 1 cytokine-biased profile in bronchoalveolar lavage fluid. Cell transfer from long-term exposed mice into hyperreactive mice also restored normal airway responsiveness, establishing the mechanism underlying the reversal of the hyperreactivity as active suppression, but did not affect eosinophilic airway inflammation. Conversely, airway hyperreactivity, suppressed as a result of long-term allergen exposure, could be reestablished by depleting T cells, in particular V4⁺ cells. Antigen-specific tolerance of ß T cells or suppression by non- T cells did not play a role in the reversal to normal airway responsiveness and T cells did not play a role in the regulation of the allergic inflammatory response. These findings show that normal responsiveness in previously hyperreactive mice, achieved after long-term allergen challenge, is based on several, apparently independent regulatory mechanisms. One of these, focused on airway responsiveness, involves active suppression and requires T cells.

Key Words: cellular activation • cytokines • mast cells/basophils • signal transduction

This article has been cited by other articles:

				L. Cook, N. Miyahara, N. Jin, J. M. Wands, C. Taube, C. L. Roark, T. A. Potter, E. W. Gelfand, R. L. O'Brien, and W. K. Born Evidence That CD8+ Dendritic Cells Enable the Development of {gamma}{delta} T Cells That Modulate Airway Hyperresponsiveness J. Immunol., July 1, 2008; 181(1): 309 - 319. [Abstract] [Full Text] [PDF]

				C. Penido, M. F. S. Costa, M. C. Souza, K. A. Costa, A. L. P. Candea, C. F. Benjamim, and M. d. G. M. O. Henriques Involvement of CC chemokines in {gamma}{delta} T lymphocyte trafficking during allergic inflammation: the role of CCL2/CCR2 pathway Int. Immunol., January 1, 2008; 20(1): 129 - 139. [Abstract] [Full Text] [PDF]

				J. Pierce, J. Rir-Sima-Ah, I. Estrada, J. Wilder, A. Strasser, and Y. Tesfaigzi Loss of pro-apoptotic Bim promotes accumulation of pulmonary T lymphocytes and enhances allergen-induced goblet cell metaplasia Am J Physiol Lung Cell Mol Physiol, November 1, 2006; 291(5): L862 - L870. [Abstract] [Full Text] [PDF]

				V. Kirtsreesakul, T. Luxameechanporn, J. J. Klemens, K. Thompson, and R. M. Naclerio Effect of genetic background on the response to bacterial sinusitis in mice. Arch Otolaryngol Head Neck Surg, October 1, 2006; 132(10): 1102 - 1108. [Abstract] [Full Text] [PDF]

				Y. Tesfaigzi Roles of Apoptosis in Airway Epithelia Am. J. Respir. Cell Mol. Biol., May 1, 2006; 34(5): 537 - 547. [Abstract] [Full Text] [PDF]

				J. M. Wands, C. L. Roark, M. K. Aydintug, N. Jin, Y.-S. Hahn, L. Cook, X. Yin, J. Dal Porto, M. Lahn, D. M. Hyde, et al. Distribution and leukocyte contacts of {gamma}{delta} T cells in the lung J. Leukoc. Biol., November 1, 2005; 78(5): 1086 - 1096. [Abstract] [Full Text] [PDF]

				N. Jin, C. Taube, L. Sharp, Y.-S. Hahn, X. Yin, J. M. Wands, C. L. Roark, R. L. O'Brien, E. W. Gelfand, and W. K. Born Mismatched Antigen Prepares {gamma}{delta} T Cells for Suppression of Airway Hyperresponsiveness J. Immunol., March 1, 2005; 174(5): 2671 - 2679. [Abstract] [Full Text] [PDF]

				R. K. Kumar, C. Herbert, D. C. Webb, L. Li, and P. S. Foster Effects of Anticytokine Therapy in a Mouse Model of Chronic Asthma Am. J. Respir. Crit. Care Med., November 15, 2004; 170(10): 1043 - 1048. [Abstract] [Full Text] [PDF]

				M. J. Tobin Asthma, Airway Biology, and Nasal Disorders in AJRCCM 2003 Am. J. Respir. Crit. Care Med., January 15, 2004; 169(2): 265 - 276. [Full Text] [PDF]