Airway hyperresponsiveness in the absence of CD4+ T cells after primary but not secondary challenge.
CD4+ T cells have been shown to play a role in the development of airway hyperresponsivness (AHR) and airway eosinophilia in mice using ablation as well as adoptive transfer experiments. However, as other T cell subsets (CD8, NKT) may play a role in these models, we examined the responses of sensitized CD4-deficient mice after either primary or secondary airway allergen challenge. After sensitization, CD4-deficiency in mice was not associated with airway eosinophilia, allergen-specific IgE, or elevated levels of interleukin (IL)-4 or IL-13. Increases in lung CD8 T cells and IL-5 were observed and shown to be essential for AHR as demonstrated after CD8 T cell depletion or anti-IL-5 treatment. In contrast to the response of sensitized CD4-deficient mice to primary allergen challenge, they failed to develop AHR after secondary allergen challenge. Although the importance of this CD4+ T cell-independent pathway in normal mice is unclear at this time, these studies identify the diversity of the cellular pathway, which may contribute to the development of AHR after primary allergen exposure of sensitized mice.
Joetham
Anthony
A
Division of Cell Biology, Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206, USA.
Takeda
Katsuyuki
K
Taube
Christian
C
Miyahara
Nobuaki
N
Kanehiro
Arihiko
A
Dakhama
Azzeddine
A
Gelfand
Erwin W
EW
D019264:Adoptive Transfer; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid; D016085:Bronchoconstrictor Agents / Q000494:pharmacology; D017252:CD3 Complex / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007073:Immunoglobulin E / Q000378:metabolism; D018793:Interleukin-13 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D016131:Lymphocyte Subsets; D016210:Methacholine Chloride / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000378:metabolism; D012130:Respiratory Hypersensitivity / Q000276:immunology*; D013601:T-Lymphocytes / Q000378:metabolism; D013997:Time Factors
D000911:Antibodies, Monoclonal; D016085:Bronchoconstrictor Agents; D017252:CD3 Complex; D018793:Interleukin-13; D015848:Interleukin-5; D016210:Methacholine Chloride; D015847:Interleukin-4; D007073:Immunoglobulin E; D010047:Ovalbumin