| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
* Department of Environmental Health, Harvard School of Public Health, Boston, MA 02115;
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA 02115; and
Department of Pathology, Brigham & Women’s Hospital, Boston, MA 02115
Immunological mechanisms leading to increased asthma susceptibility in early life remain obscure. In this study, we examined the effects of neonatal Ab treatments targeting T cell populations on the development of an asthma syndrome. We used a model of increased asthma susceptibility where offspring of asthmatic BALB/c mother mice are more prone (than normal pups) to develop the disease. Neonatal pretreatment of naive pups with mAb directed against the IL-2R
chain (CD25), the costimulatory molecule glucocorticoid-induced TNFR family related gene, and the inhibitory molecule CTLA-4 elicited contrasting effects in offspring depending on the mother’s asthma status. Specifically, neonatal CD25high T cell depletion stimulated asthma susceptibility in normal offspring whereas it ameliorated the condition of pups born of asthmatic mothers. Conversely, glucocorticoid-induced TNFR family related gene ligation as a primary signal reduced the spleen cellularity and largely abrogated asthma susceptibility in asthma-prone offspring, without inducing disease in normal pups. Striking changes in Th1/Th2 cytokine levels, especially IL-4, followed mAb pretreatment and were consistent with the impact on asthma susceptibility. These results point to major differences in neonatal T cell population and responsiveness related to maternal asthma history. Interventions that temporarily remove and/or inactivate specific T cell subsets may therefore prove useful to attenuate early life asthma susceptibility and prevent the development of Th2-driven allergic airway disease.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by the National Institutes of Health Grant HL69760.
2 Current address: Momenta Pharmaceuticals, 675 West Kendall Street, Cambridge, MA 02142.
3 Address correspondence and reprint requests to Dr. Lester Kobzik, Department of Environmental Health, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115. E-mail address: lkobzik{at}hsph.harvard.edu
4 Abbreviations used in this paper: AHR, airway hyperresponsiveness; Treg, regulatory T cell; GITR, glucocorticoid-induced TNFR family-related gene; 7-AAD, 7-aminoactinomycin D; MCh, methacholine chloride; Penh, enhanced pause; BAL, bronchoalveolar lavage.
This article has been cited by other articles:
|
|
 |
|
  G. T. Schnickel, S. Bastani, G. R. Hsieh, A. Shefizadeh, R. Bhatia, M. C. Fishbein, J. Belperio, and A. Ardehali Combined CXCR3/CCR5 Blockade Attenuates Acute and Chronic Rejection J. Immunol., April 1, 2008; 180(7): 4714 - 4721. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Mitzner Counterpoint: Lung Impedance Measurements are not More Useful than Simpler Measurements of Lung Function in Animal Models of Pulmonary Disease J Appl Physiol, November 1, 2007; 103(5): 1901 - 1903. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
