Chemoattractant mechanism of Th1 cells in class III and IV lupus nephritis.
Proliferative lupus nephritis (PLN) is the common, severe, and important form of lupus nephritis. Recent report showed that T cells producing Interferon (IFN)gamma (Th1 cells) increased in patients with World Health Organization class IV. However, the relation between the increase of Th1 cells and the pathogenesis has been made unclear. The aim of this study was to examine the chemoattractant mechanism of Th1-producing cells and whether in vitro IFNgamma secretion from Th1-producing cells in PLN. The Th1:Th2 ratio in peripheral blood was measured by flow cytometry. The serum levels of IL-2, IFNgamma, IL-13, monocyte chemoattractant protein-1 (MCP-1) and IP-10 were determined by using enzyme-linked immunosorbent assay. In in vitro IFNgamma production assay, CD4(+)T cells co-cultured with IL-12 and/or IL-18. Th1:Th2 ratio in PLN was high and not correlated with the serum Th1 cytokine level. This Th1-producing cell tended to go toward the inflammatory lesion by low CD62L expression and chemokines. The level of MCP-1 and IP-10 in patients with PLN significantly increased. Lastly, in vitro IFNgamma production assay, patients with PLN CD4(+)T cells produced IFNgamma by the addition of IL-12 and IL-18, while CD4(+)T cells in normal controls did not produce. These findings suggest that combination of Th1 inducers and chemokine inhibition might be powerful threrapeutic approach in PLN.
Morimoto
Shinji
S
Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, Tokyo, Japan. morimoto@juntendo.ac.jp
Tokano
Yoshiaki
Y
Nakano
Souichiro
S
Watanabe
Takashi
T
Tamayama
Yoshihiro
Y
Mitsuo
Akiko
A
Suzuki
Jun
J
Kaneko
Hiroshi
H
Sekigawa
Iwao
I
Takasaki
Yoshinari
Y
D000293:Adolescent; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018932:Chemokine CCL2 / Q000097:blood; D054357:Chemokine CXCL10 / Q000097:blood; D018925:Chemokines / Q000097:blood / Q000276:immunology*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology*; D018664:Interleukin-12 / Q000494:pharmacology; D018793:Interleukin-13 / Q000097:blood; D020382:Interleukin-18 / Q000494:pharmacology; D007376:Interleukin-2 / Q000097:blood; D007378:Interleukins / Q000097:blood / Q000276:immunology*; D019041:L-Selectin / Q000276:immunology / Q000378:metabolism; D008181:Lupus Nephritis / Q000097:blood / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D018417:Th1 Cells / Q000276:immunology* / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology; D055815:Young Adult
C111835:CCL2 protein, human; C114753:CXCL10 protein, human; D018932:Chemokine CCL2; D054357:Chemokine CXCL10; D018925:Chemokines; C508594:IL2 protein, human; D018793:Interleukin-13; D020382:Interleukin-18; D007376:Interleukin-2; D007378:Interleukins; D019041:L-Selectin; D018664:Interleukin-12; D007371:Interferon-gamma