Abstracts from the Conjoint Annual Meeting of L’Association des pneumologues de la province de Québec and le Réseau en santé respiratoire du FRSQ

摘要

We previously observed the lungs of naïve BALBc/J Cftrtm1UNC mice to have greater numbers of lymphocytes, by immunohistochemical staining, than did BALB wild-type littermates or C57BL/6J Cftrtm1UNC mice. Herein, we initially investigated whether this mutation in Cftr alters the adaptive immunity phenotype by measuring the lymphocyte populations in the lungs and spleens by FACS and by evaluating CD3 stimulated cytokine secretion, proliferation and apoptosis responses. Next we assessed a potential influence of this lymphocyte phenotype on lung function through airway resistance measures. Finally, we mapped the phenotype of pulmonary lymphocyte counts in BALB×C57BL/6J F2 Cftrtm1UNC mice and reviewed positional candidate genes. By FACS analysis both the lungs and spleens of BALB Cftrtm1UNC mice had more CD3+ (both CD4+ and CD8+) cells than did littermates or C57BL/6J Cftrtm1UNC mice. Cftrtm1UNC and littermate mice of either strain did not differ in anti-CD3 stimulated apoptosis or proliferation levels. Lymphocytes from BALB Cftrtm1UNC mice produced more Il-4 and Il-5 and reduced levels of interferon-γ than littermates while lymphocytes from C57BL/6J Cftrtm1UNC mice demonstrated increased Il-17 secretion. BALB Cftrtm1UNC mice presented an enhanced airway hyperresponsiveness to methacholine challenge compared to littermates and C57BL/6J Cftrtm1UNC mice. A chromosome 7 locus was identified to be linked to lymphocyte numbers and genetic evaluation of the interval suggests integrinαL and Il4ra as candidate genes for this trait. We conclude that the pulmonary phenotype of BALB Cftrtm1UNC mice includes airway hyper-responsiveness and increased lymphocyte numbers with the latter trait influenced by a chromosome 7 locus.