Adoptive transfer of T cells induces airway hyperresponsiveness independently of airway eosinophilia but in a signal transducer and activator of transcription 6-dependent manner.
BACKGROUND
Activated T cells, through the release of specific cytokines (ie, IL-4, IL-5, and IL-13), regulate effector cell recruitment and function. In this way T cells orchestrate the inflammatory response, which leads to airway hyperresponsiveness (AHR), a cardinal feature of allergic asthma.


OBJECTIVE
In the present study the direct role of T cells and, in particular, the importance of signal transducer and activator of transcription 6 (STAT6) in T cells was investigated in the development of AHR.


METHODS
In a murine model of allergen-driven AHR, the effects of adoptive transfer of STAT6-containing (STAT6+/+) and STAT6-deficient (STAT6-/-) T cells from sensitized mice into allergen-challenged mice were tested.


RESULTS
Although greater in STAT6+/+ mice, both allergen-challenged STAT6+/+ and STAT6-/- mice had AHR after transfer of T cells from sensitized STAT6+/+ mice. In contrast, AHR did not develop in allergen-challenged STAT6-/- mice after transfer of T cells from sensitized STAT6-/- mice. Reconstitution of AHR after T-cell transfer was not associated with airway eosinophilia.


CONCLUSIONS
The data indicate that the STAT6 status of the donor mice is critical to the development of AHR. Although not critical for the development of AHR, the STAT6 status of the recipient mice might play a contributory-regulatory role in the AHR response. The results identify a STAT6-dependent T-cell pathway capable of modulating airway responsiveness, even in the absence of a significant airway eosinophilia.
Tomkinson
Adrian
A
Division of Cell Biology, the Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colo 80206, USA.
Duez
Catherine
C
Lahn
Michael
M
Gelfand
Erwin W
EW
D019264:Adoptive Transfer; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D016207:Cytokines / Q000032:analysis; D004802:Eosinophilia / Q000473:pathology; D005260:Female; D007114:Immunization; D008297:Male; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D010047:Ovalbumin / Q000276:immunology; D050800:STAT6 Transcription Factor; D013601:T-Lymphocytes / Q000637:transplantation*; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*
D016207:Cytokines; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D010047:Ovalbumin