Antigen-stimulated lung CD4+ cells produce IL-5, while lymph node CD4+ cells produce Th2 cytokines concomitant with airway eosinophilia and hyperresponsiveness.
OBJECTIVE
We investigated whether airway inflammation in a mouse model of allergic asthma is related to antigen-specific T cell responses in the effector organ, the lung, and in the lung draining lymph nodes (LN).


METHODS
In BALB/c mice pathophysiological parameters were measured in vivo, and lung draining LN and lung cells were restimulated in vitro.


METHODS
Mice were sensitized with ovalbumin and repeatedly challenged with ovalbumin or saline inhalation.


METHODS
Airway reactivity, inflammation in the airways, serum levels of IgE were measured, and cytokine levels and proliferative responses were determined in antigen-stimulated lymphocyte cultures.


CONCLUSIONS
Sensitization results in antigen-specific Th0-like LN cells, despite the presence of antigen-specific IgE. Repeated antigen inhalation induced airway hyperresponsiveness and eosinophil infiltration concomitant with a shift towards Th2 cytokine production exclusively by lung draining LN T cells. Furthermore, these airway symptoms are associated with antigen-specific CD4+ effector T cells in the airway tissue producing only IL-5, but not IL-4, which are unable to proliferate.
Hofstra
C L
CL
Department of Pharmacology and Pathophysiology, Utrecht University, The Netherlands. Chofstra@prius.jnj.com
Van Ark
I
I
Nijkamkp
F P
FP
Van Oosterhout
A J
AJ
D000818:Animals; D016535:Bronchial Hyperreactivity / Q000378:metabolism* / Q000503:physiopathology; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis*; D004802:Eosinophilia / Q000378:metabolism*; D005434:Flow Cytometry; D007073:Immunoglobulin E / Q000096:biosynthesis; D007202:Indicators and Reagents; D015848:Interleukin-5 / Q000096:biosynthesis*; D008168:Lung / Q000166:cytology / Q000378:metabolism*; D008198:Lymph Nodes / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D018418:Th2 Cells / Q000187:drug effects / Q000378:metabolism*
D016207:Cytokines; D007202:Indicators and Reagents; D015848:Interleukin-5; D007073:Immunoglobulin E