T regulatory cells are markedly diminished in diseased salivary glands of patients with primary Sjögren's syndrome

Abstract

Objective: To investigate the abnormalities of T regulatory cells (Treg) in salivary glands and peripheral blood in patients with primary Sjögren's syndrome (pSS).

Methods: Levels of CD4+CD25+ high T cells of the peripheral blood of 52 patients with pSS were measured by flow-cytometric assay. Lower lip salivary gland biopsies were examined by immunohistochemistry, using monoclonal mouse anti-human antibodies [CD25, CD4, CD8, CD68, forkhead transcription factor (Foxp3)] in 30 patients with pSS. Using real-time polymerase chain reaction, Foxp3 messenger RNA expression was assessed in the salivary glands and CD4+ T cells from peripheral blood.

Results: Many inflammatory cells, predominantly CD4+ and CD8+ T cells and macrophages, were found in salivary glands of patients with SS, but CD4+CD25+ Treg numbers and Foxp3 expression were markedly reduced in those biopsy samples. Levels of CD4+CD25+ high T cells and Foxp3 expression in peripheral blood of patients with pSS were significantly lower than in healthy controls. However, the inhibitory function of CD4+CD25+ T cells in pSS was unchanged compared to that of controls. Peripheral CD4+CD25+ high T cell numbers in pSS did not correlate with Schirmer's test and salivary flow rate, or with the presence or absence of anti-SSA/SSB antibodies and immunoglobulin level.

Conclusion: The remarkable reduction of Treg numbers in salivary glands and reduction of CD4+CD25+ high T cells in peripheral blood suggests a possible role for absence of Treg in the pathogenesis of salivary gland destruction in pSS.