Foxp3 expressing CD4+ CD25+ and CD8+CD28- T regulatory cells in the peripheral blood of patients with lung cancer and pleural mesothelioma.

The role of T regulatory (Treg) cells in human cancer has not yet been clarified. We assessed the presence and function of CD4+ and CD8+ Treg cell subsets in the peripheral blood of patients with lung cancer (LC) and pleural mesothelioma (PM). We found a low but significant increase in the number of CD4+ T cells with phenotype and functional features of Treg cells in LC patients compared to normal healthy controls (NHC). Furthermore, total CD4+ T cells from LC patients proliferated less than cells from controls, suggesting that the increase in the CD4+ Treg cell pool has functional importance. LC patients also showed an expansion of the CD8+CD28- T cell subset and these cells expressed Foxp3 mRNA, as recently observed in alloantigen-specific CD8+CD28- T suppressor cells. No variation of peripheral Treg cell subsets was found in patients with PM, a disease with a predominantly localized nature. However, the lack of correlation between cancer stage and the number or the function of peripheral Treg cells in LC patients refuted the hypothesis that these cells are involved in tumor spreading. A possible involvement of the peripheral Treg cell pool in cancer development and/or in inducing systemic immunosuppression in LC patients can be hypothesized.

Complement receptor 1 gene polymorphisms are associated with idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic, fibrotic disorder underlain by aberrant wound healing of repeated lung injury. Environmental triggers and genetic background are likely to act as modifiers of the fibrotic response. Erythrocyte complement receptor 1 is a membrane protein mediating the transport of immune complexes to phagocytes. Three gene polymorphisms are related to the erythrocyte surface density of complement receptor 1 molecules, which in turn are related to the rate of immune complexes' clearance. There is evidence of association between sarcoidosis and the complement receptor 1 gene. We wondered whether IPF is associated with the complement receptor 1 gene alleles coding for a reduced molecule/erythrocyte ratio. We studied 74 patients and 166 control subjects. Three polymorphic sites of the gene, A3650G exon 22, HindIII RFLP intron 27, and C5507G exon 33, were analyzed and found to be in linkage disequilibrium. The GG genotype for the C5507G exon 33 polymorphism was significantly more common in patients with IPF than in control subjects (odds ratio = 6.232, 95% confidence interval = 2.198-18.419, p = 0.00023). The significant difference was found in both sexes. These findings agree with speculations on the role of the complement receptor 1 gene in idiopathic pulmonary fibrosis.