T cells from human allergen-induced late asthmatic responses express IL-12 receptor beta 2 subunit mRNA and respond to IL-12 in vitro.
IL-12 suppresses proallergic Th2-type cytokine production and induces Th1-type cytokine production by peripheral blood T cells from subjects with allergic disease. The objective of the present study was to examine the relevance of these findings to target organ T cell responses in human asthma. Bronchoalveolar lavage (BAL) and PBMC were collected from atopic asthmatics 24 h after fiberoptic allergen challenge of a segmental bronchus. BAL T cells and PBMC were cultured with allergen in the presence of recombinant IL-12 or IFN-gamma, and cytokines were measured in culture supernatants after 6 days. IL-5 production by BAL T cells and PBMC was inhibited by IL-12 and, to a lesser extent, by IFN-gamma. IL-12 also induced IFN-gamma production by BAL T cells and PBMC. The effects of IL-12 nor IFN-gamma on IL-5 production could not be reversed by neutralizing anti-IFN-gamma or anti-IL-12 mAbs, respectively. Thus, the effect of neither IL-12 nor IFN-gamma appeared to be mediated through induction of the other cytokine. In situ hybridization revealed that approximately one-third of BAL T cells expressed mRNA transcripts encoding the IL-12R beta 2 subunit following allergen challenge. Thus, human T cells obtained from BAL during asthmatic late responses, like T cells in the peripheral circulation, remain susceptible to immunomodulation by IL-12. These findings raise the possibility that IL-12 may hold therapeutic potential in allergic diseases such as asthma.
Varga
E M
EM
Upper Respiratory Medicine, Imperial College School of Medicine at National Heart and Lung Institute, London, United Kingdom.
Wachholz
P
P
Nouri-Aria
K T
KT
Verhoef
A
A
Corrigan
C J
CJ
Till
S J
SJ
Durham
S R
SR
D000328:Adult; D000485:Allergens / Q000008:administration & dosage*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001249:Asthma / Q000276:immunology* / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D002999:Clone Cells; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000276:immunology / Q000494:pharmacology; D018664:Interleukin-12 / Q000378:metabolism / Q000494:pharmacology*; D015848:Interleukin-5 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000097:blood; D008297:Male; D008925:Mites / Q000276:immunology; D011058:Pollen / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis*; D018123:Receptors, Interleukin / Q000096:biosynthesis* / Q000235:genetics; D053707:Receptors, Interleukin-12; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D013997:Time Factors
D000485:Allergens; D000911:Antibodies, Monoclonal; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D015848:Interleukin-5; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D018664:Interleukin-12; D007371:Interferon-gamma