Differential roles for CD4 and CD8 T cells after diisocyanate sensitization: genetic control of TH2-induced lung inflammation.
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
Mice were epicutaneously exposed to HDI and then challenged with HDI, either by means of inhalation to induce airway inflammation or on the ear to induce contact hypersensitivity (CHS). Lymph node cytokine production and serum antibodies were also measured.


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.


CONCLUSIONS
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.
Departments of Dermatology, Immunobiology, and Internal Medicine, Yale University School of Medicine, New Haven, CT 06520-8059, USA.
Christina A
CA
Herrick
Jyoti
J
Das
Lan
L
Xu
Adam V
AV
Wisnewski
Carrie A
CA
Redlich
Kim
K
Bottomly
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D003485:Cyanates / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D003877:Dermatitis, Contact / Q000235:genetics; D007074:Immunoglobulin G / Q000097:blood; D017953:Isocyanates; D051379:Mice; D008815:Mice, Inbred Strains; D009687:Nuclear Proteins; D011657:Pulmonary Eosinophilia / Q000139:chemically induced* / Q000235:genetics*; D013045:Species Specificity; D018418:Th2 Cells / Q000276:immunology*; D015534:Trans-Activators / Q000502:physiology; D001613:beta 2-Microglobulin / Q000502:physiology
D003485:Cyanates; D016207:Cytokines; D007074:Immunoglobulin G; D017953:Isocyanates; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D015534:Trans-Activators; D001613:beta 2-Microglobulin; C015262:1,6-hexamethylene diisocyanate