Peripheral blood regulatory T cells from silicosis patients are susceptible to CD95-mediated apoptosis.
Given that silicosis patients (SILs) suffer not only from pulmonary fibrosis but also from complications associated with autoimmune diseases such as rheumatoid arthritis and systemic sclerosis, silica may have the effect of disturbing self-tolerance. One advancement in the field of immunoregulation concerned discovery of the regulatory T (Treg) cell, characterized as CD4+CD25+ and FoxP3+. Treg cells regulate the activation of responder T cells, and a reduction in the size (absolute and/or relative number) and function of Treg cells leads to excessive activation of responder T cells against various antigens including self-antigens. This mechanism may be associated with the occurrence of autoimmune diseases. Our previous investigations showing reduced Treg cell function in the CD4+CD25+ fraction of SILs indicated alterations of Treg cell size or function. Here, we examined the expression of pd- 1, a T cell activation marker, in CD4+CD25- and CD4+CD25+ fractions, expression of surface CD95 known as Fas, an apoptosis inducing receptor, in Treg cells, and susceptibility against apoptosis inducing anti-CD95 antibody in CD4+CD25- and CD4+CD25+ cells. We observed chronic activation of responder T and Treg cells in SILs, higher expression of CD95 and higher susceptibility to the CD95 stimulating antibody in Treg cells from SILs. Taken together, the reduction of Treg cell function and size caused by excessive loss of Treg cells and substitution by chronically activated responder T cells caused by silica exposure may be important in facilitating the disturbance of autoimmunity in SILs. (Accepted on Octorber 6, 2009)