Selective accumulation of CCR4+ T lymphocytes into renal tissue of patients with lupus nephritis.
OBJECTIVE
Some chemokine receptors, such as CCR5 and CCR4, are differentially expressed on Th1 and Th2 cells. To determine whether differential expression of the chemokine receptors occurs in patients with lupus nephritis, we examined the expression of CCR4 and CCR5 on peripheral blood lymphocytes and mononuclear cells infiltrated into the renal tissue of patients with lupus nephritis.


METHODS
The expression of CCR4 and CCR5 on CD4+,CD45RO+ cells was analyzed by flow cytometry and compared between patients with systemic lupus erythematosus (SLE) and healthy controls. Correlation between the absolute number of CCR4+ or CCR5+ cells and clinical parameters was also analyzed. Mononuclear infiltrates in the renal tissue of SLE patients were analyzed for the expression of CCR4, CCR5, and CD4 by immunohistochemical staining.


RESULTS
The absolute number of CCR4+, but not CCR5+, T lymphocytes in the peripheral blood was significantly decreased in the patients with SLE compared with that in the healthy controls, and this positively correlated with the serum levels of C3 and CH50. Most of the CD4+ T lymphocytes that infiltrated into the renal tissue of the patients with lupus nephritis expressed CCR4, but not CCR5.


CONCLUSIONS
These results suggest that CCR4+ T lymphocytes in peripheral blood, which represent Th2 cells, preferentially migrate into the renal tissue of patients with lupus nephritis. The maldistribution of CCR4+ T lymphocytes might be involved in the pathogenesis of lupus nephritis.
Yamada
Masato
M
Department of Rheumatology, Juntendo University School of Medicine, Tokyo, Japan. yamada@joy.ocn.ne.jp
Yagita
Hideo
H
Inoue
Hideko
H
Takanashi
Tsuyoshi
T
Matsuda
Hironori
H
Munechika
Eiko
E
Kanamaru
Yutaka
Y
Shirato
Isao
I
Tomino
Yasuhiko
Y
Matushima
Kouji
K
Okumura
Ko
K
Hashimoto
Hiroshi
H
D000293:Adolescent; D000328:Adult; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D005260:Female; D006801:Humans; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000378:metabolism / Q000473:pathology; D008181:Lupus Nephritis / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D054398:Receptors, CCR4; D019707:Receptors, Chemokine / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism*
C515354:CCR4 protein, human; D054398:Receptors, CCR4; D019707:Receptors, Chemokine; D017493:Leukocyte Common Antigens