Abstract | BACKGROUND: Exposure to diisocyanates is a major cause of occupational asthma. We previously developed a novel mouse model of diisocyanate-induced asthma involving epicutaneous sensitization to hexamethylene diisocyanate (HDI) that demonstrates many features of the human disease, including airway eosinophilia and mucus hypersecretion. OBJECTIVE: To determine what factors are critical for the development of HDI-induced airway inflammation, we investigated the strain distribution of this response and the roles of CD4(+) and CD8(+) T cells. METHODS: RESULTS: Induction of airway eosinophilia was highly dependent on the mouse strain used, with C57BL/6, A/J, CBA, C3H, and C57BL/10 mice all having significantly fewer eosinophils than BALB/c mice. HDI-specific antibodies and lymph node IL-5 and IL-13 production were also diminished in non-BALB/c strains. In contrast, CHS to HDI developed in all strains tested. Studies in mice deficient in either CD4(+) or CD8(+) T cells revealed that CD4(+) T cells were critical for HDI-induced airway eosinophilia, whereas CD8(+) T cells were the major effector cells in CHS. CONCLUSION: The data suggest that, in contrast to CHS, induction of T(H)2 responses after epicutaneous exposure to diisocyanates is strongly genetically influenced. Furthermore, the lung inflammatory response to inhaled HDI appears to depend primarily on effective generation of these CD4(+) T(H)2 responses, as is the case in atopic asthma.
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Authors | Christina A Herrick, Jyoti Das, Lan Xu, Adam V Wisnewski, Carrie A Redlich, Kim Bottomly |
Journal | The Journal of allergy and clinical immunology
(J Allergy Clin Immunol)
Vol. 111
Issue 5
Pg. 1087-94
(May 2003)
ISSN: 0091-6749 [Print] United States |
PMID | 12743574
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Cyanates
- Cytokines
- Immunoglobulin G
- Isocyanates
- MHC class II transactivator protein
- Nuclear Proteins
- Trans-Activators
- beta 2-Microglobulin
- 1,6-hexamethylene diisocyanate
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Topics |
- Animals
- CD4-Positive T-Lymphocytes
(physiology)
- CD8-Positive T-Lymphocytes
(physiology)
- Cyanates
(immunology)
- Cytokines
(biosynthesis)
- Dermatitis, Contact
(genetics)
- Immunoglobulin G
(blood)
- Isocyanates
- Mice
- Mice, Inbred Strains
- Nuclear Proteins
- Pulmonary Eosinophilia
(chemically induced, genetics)
- Species Specificity
- Th2 Cells
(immunology)
- Trans-Activators
(physiology)
- beta 2-Microglobulin
(physiology)
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