HLA class II antigens and T lymphocytes in human nasal epithelial cells. Modulation of the HLA class II gene transcripts by gamma interferon.

BACKGROUND

Nasal polyps are characterized by a proliferation of the epithelial layer of the mucosa, cellular infiltrates and other pathological changes; however the mechanisms involved in polyp pathogenesis remain largely unclear.

OBJECTIVES

We have taken two different approaches to study the cellular events involved in nasal polyposis.

METHODS

First, through use of immunohistochemical methods, we have studied the expression of HLA class II antigens in epithelial cells of nasal polyps and the distribution of lymphocytes in the epithelium and in the subepithelial layer in patients with clinical conditions, such as asthma, atopy, aspirin intolerance or cystic fibrosis, and in subjects with an absence of concomitant diseases. Second, in order to investigate whether HLA class II expression is controlled at the pre- or post-transcriptional level, we studied the effect of interferon gamma (INF gamma) on epithelial cells in primary culture, which were derived from HLA class II negative and HLA class II positive nasal polyps. Total RNA was extracted from the cells and reverse-transcribed, and the c-DNA corresponding to DR, DP, DQ loci was amplified by PCR.

RESULTS

Expression of HLA class II antigens by the epithelia of nasal polyps was more common in the presence rather than in the absence of concomitant asthma, atopy or cystic fibrosis (59% versus 40%). HLA-DR was the only HLA class II antigen expressed in the seven polyps taken from cystic fibrosis patients. The number of CD8+ cells was significantly higher in polyps associated with known clinical conditions and HLA class II antigen expression than it was in 'isolated' polyps and in HLA class II negative polyps. RNA transcripts for at least one or all three HLA-DR, DP and DQ antigens were detected in 10 cultures of the II HLA class II positive polyps. Conversely, 8 of 10 cultures derived from HLA class II negative polyps did not express HLA class II transcripts in the absence of INF gamma. Adding INF gamma (100 U/ml) to the latter cell cultures caused expression of transcripts of one or more HLA class II genes.

CONCLUSIONS

We have shown that HLA class II antigens were more frequently detected in polyps of patients with an identified clinical syndrome than in those of asymptomatic subjects. Our results also suggest that IFN gamma regulates expression of HLA class II antigens in airway epithelial cells of the nasal polyps at the transcriptional level, and that cultured cells from nasal polyps represent a suitable model to investigate immune mechanisms involved in diseases such as atopy, asthma and cystic fibrosis.