| First Author | Soltys J | Year | 2002 |
| Journal | J Immunol | Volume | 168 |
| Issue | 4 | Pages | 1903-10 |
| PubMed ID | 11823525 | Mgi Jnum | J:74476 |
| Mgi Id | MGI:2158530 | Doi | 10.4049/jimmunol.168.4.1903 |
| Citation | Soltys J, et al. (2002) Functional IL-10 deficiency in the lung of cystic fibrosis (cftr(-/-)) and IL-10 knockout mice causes increased expression and function of B7 costimulatory molecules on alveolar macrophages. J Immunol 168(4):1903-10 |
| abstractText | Alveolar macrophages are poor APCs that only minimally express B7 costimulatory molecules. Because our previous data suggest that bronchial epithelial cells constitutively secrete IL-10, and IL-10 inhibits B7 expression in vitro, we hypothesized that this IL-10 is responsible for suppressing B7 expression on macrophages that enter the airways. Furthermore, because we have shown that cystic fibrosis (CF) lungs are deficient in IL-10, we hypothesized that bronchoalveolar macrophages (BALMs) from cystic fibrosis transmembrane conductance regulator (CFTR)(-/-) as well as IL-10(-/-) mice might express increased B7. Immunofluorescence for B7 was positive on BALMs from CF patients and CFTR(-/-) and IL-10(-/-) mice, but was negative on controls. FACS showed that 63.9% of BALMs from IL-10(-/-) mice were B7-1 positive, as were 67.4% of BALMs from CFTR(-/-) mice, whereas <7% of BALMs from wild-type controls were positive. Using BALMs to costimulate splenic T cells with anti-CD3 as a mitogen showed 9202 +/- 2107 cpm [(3)H]thymidine incorporation for BALMs from IL-10(-/-) mice and 4082 +/- 1036 cpm for BALMs from CFTR(-/-) mice, but <200 cpm with BALMs from either type of +/+ mouse. Treatment of CFTR(-/-) mice with recombinant mouse IL-10 reduced the B7 expression and costimulatory activity of the BALMs. These data suggest that the IL-10 secreted in the healthy lung may be responsible for the absence of B7 and poor costimulatory activity of BALMs and that reductions of pulmonary IL-10 in CF may enhance B7 expression and local immune responses. |
