Distribution of CXCR3- or CCR4-positive cells in interstitial pneumonia associated with primary Sjogren's syndrome.
Patients with primary Sjogren's syndrome (SS) occasionally develop interstitial pneumonia (SS-IP), the prognosis of which is less grave compared with that of idiopathic pulmonary fibrosis (IPF). We examined distribution of helper T-cell subsets in open lung biopsy specimens from seven patients with SS-IP and, for comparison, ten patients with IPF. The expression of CXCR3 and CCR4, chemokine receptors associated in vitro with Th1 and Th2 cells, respectively, was analyzed in the mononuclear infiltrate using immunohistochemistry. The expression of CD4, CD8, and CD20 in the infiltrate was similarly examined. The positive cells were semiquantified in fibrosing areas and lymphoid clusters of both SS-IP and IPF. In fibrosing areas, CXCR3-positive cells were dominant over CCR4-positive cells in all cases of SS-IP, whereas the two types of cells showed no such difference in cases of IPF. Each of the CXCR3/CD4 and CXCR3/CCR4 ratios was significantly higher in SS-IP than in IPF ( P<0.05 and P<0.05, respectively). The CCR4/CD4 ratio showed a significantly lower value in SS-IP than in IPF ( P<0.05). In lymphoid clusters, prominent in SS-IP and few and small in IPF, CXCR3-positive cells predominated over CCR4-positive cells in both lung lesions. There was no significant difference of CXCR3/CCR4 ratio in lymphoid clusters between SS-IP and IPF ( P=0.33). These findings in SS-IP are in accordance with those reported in previous studies of the salivary glands of SS patients, where most of the infiltrating lymphocytes expressed CXCR3, and the expression of interferon-gamma was upregulated. In contrast, the Th2 cell dominance was reported in IPF in the previous studies. The present findings suggest that the pathogenesis of interstitial pneumonia is different between SS-IP and IPF in regard to the roles of helper T-cell subsets.
Shimizu
Shigeki
S
Department of Pathology, Nagoya City University Medical School, Mizuho-ku, 467-8601 Nagoya, Japan. shimizsh@med.nagoya-cu.ac.jp
Yoshinouchi
Takeo
T
Naniwa
Taio
T
Nakamura
Mikae
M
Sato
Shigeki
S
Ohtsuki
Yuji
Y
Fujita
Jiro
J
Yamadori
Ichiro
I
Eimoto
Tadaaki
T
Ueda
Ryuzo
R
D000368:Aged; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017563:Lung Diseases, Interstitial / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D054398:Receptors, CCR4; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000032:analysis*; D012859:Sjogren's Syndrome / Q000276:immunology*
C515354:CCR4 protein, human; C515187:CXCR3 protein, human; D016207:Cytokines; D054398:Receptors, CCR4; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine