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


CONCLUSIONS
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.
Li
Xiaomei
X
Department of Rheumatology and Immunology, Anhui Medical University Affiliated Provincial Hospital, Hefei, Anhui Province, China. Lixiaomei1@medmail.com.cn
Li
Xiangpei
X
Qian
Long
L
Wang
Guosheng
G
Zhang
Hong
H
Wang
Xiaoqiu
X
Chen
Ke
K
Zhai
Zhimin
Z
Li
Qing
Q
Wang
Yiping
Y
Harris
David C H
DC
D000328:Adult; D001707:Biopsy, Needle; D015704:CD4 Antigens / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000096:biosynthesis; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000097:blood; D008297:Male; D008875:Middle Aged; D012469:Salivary Glands / Q000473:pathology*; D012859:Sjogren's Syndrome / Q000097:blood / Q000473:pathology*; D016176:T-Lymphocyte Subsets; D050378:T-Lymphocytes, Regulatory
D015704:CD4 Antigens; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit