TH1-mediated airway hyperresponsiveness independent of neutrophilic inflammation.
BACKGROUND
T(H)2-mediated allergic asthma is characterized by eosinophilia, mucus overproduction, and airway hyperresponsiveness (AHR). Although it is clear that T(H)2 cells and their cytokines play an important role in AHR, the roles of T(H)1 cells and neutrophils in AHR are controversial.


OBJECTIVE
We sought to determine the roles of T(H)1 cells and neutrophils in AHR.


METHODS
Ovalbumin-specific CD4(+) T cells were purified from DO11.10 mice, differentiated into T(H)1 cells, and injected into naive BALB/c, IL-4RalphaKO, or IL-8RKO mice. After ovalbumin antigen challenge, cytokine mRNA levels in lung samples, as well as inflammatory cell types and numbers in bronchoalveolar lavage fluid (BALF), were determined. AHR was assessed by measuring resistance in tracheostomized mice and enhanced pause in freely moving mice.


RESULTS
T(H)1 cells induced AHR as robust as T(H)2 cells. They also induced lung inflammation dominated by neutrophils. Neither AHR nor inflammation were reduced when T(H)1 cells were transferred into IL-4RalphaKO mice. When IL-8RKO mice were used as recipients of T(H)1 cells, neutrophilia was greatly reduced, but the AHR was as strong as that seen in wild-type mice. On the other hand, dexamethasone treatment had no effect on neutrophilia but has significantly reduced AHR. Reduction in AHR was accompanied by a reduction in the numbers of lymphocytes and macrophages in BALF.


CONCLUSIONS
T(H)1 cells can induce strong AHR independent of IL-4 and IL-13. The AHR is associated with the presence of lymphocytes and macrophages, but not neutrophils, in BALF. Our results point to a pathway whereby T(H)1 cells mediate AHR independent of neutrophilic inflammation.
Cui
Junqing
J
Wyeth Research, Cambridge, MA 02140, USA. jcui@wyeth.com
Pazdziorko
Stephen
S
Miyashiro
Joy S
JS
Thakker
Paresh
P
Pelker
Jeffrey W
JW
Declercq
Charlene
C
Jiao
Aiping
A
Gunn
Jason
J
Mason
Lawrence
L
Leonard
John P
JP
Williams
Cara M M
CM
Marusic
Suzana
S
D019264:Adoptive Transfer; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D001991:Bronchitis / Q000473:pathology*; D016207:Cytokines / Q000235:genetics; D003907:Dexamethasone / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology; D018793:Interleukin-13 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009093:Mucus / Q000378:metabolism; D009504:Neutrophils / Q000473:pathology*; D010047:Ovalbumin / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D023062:Receptors, Interleukin-8A / Q000172:deficiency; D012720:Severity of Illness Index; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology
D016207:Cytokines; D005938:Glucocorticoids; D018793:Interleukin-13; D012333:RNA, Messenger; D023062:Receptors, Interleukin-8A; D003907:Dexamethasone; D010047:Ovalbumin