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2002 Fiscal Year Final Research Report Summary

Analysis of Thl/Th2 imbalance of systemic lupus erythematosus

Research Project

Project/Area Number 11670458
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 内科学一般
Research InstitutionJuntendo University

Principal Investigator

YAMADA Masato  Juntendo University, School of Medicine, Dept. of Rheumatology, Assistant Professor, 医学部, 講師 (90311977)

Co-Investigator(Kenkyū-buntansha) TAMURA Naoto  Juntendo University, School of Medicine, Dept. of Rheumatology, Assistant Professor, 医学部, 講師 (20227284)
FUKAZAWA Toru  Juntendo University, School of Medicine, Dept. of Rheumatology, Assistant Professor, 医学部, 講師 (30301500)
YAGITA Hideo  Juntendo University, School of Medicine, Dept. of Immunology, Associate Professor, 医学部, 助教授 (30182306)
Project Period (FY) 1999 – 2002
KeywordsSystemic Lupus Erythemotosus / Lupus Nephritis / Th1 / Th2 / Chemokine Receptor / CCR5 / CCR4 / sjogren's syndrome
Research Abstract

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 was observed in patients with lupus nephritis, we examined the expression of CCR4 and CCR5 on peripheral blood lymphocytes and mononuclear cells infiltrated into 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 (PB) was significantly decreased in the patients with SLE compared to that in healthy controls and positively correlated with the serum levels of 3rd component of complement (C3) and 50% hemolytic unit of complement (CH50). Most of the CD4^+ T lymphocytes that infiltrated into the renal tissue of the patients with lupus nephritis expressed CCR4 but not CCR5
Conclusion; These results suggested that CCR4^+ T lymphocytes in PB, which represent Th2 cells, preferentially migrated into the renal tissue of the patients with lupus nephritis. The maldistribution of CCR4^+ T lymphocytes might be involved in the pathogenesis of lupus nephritis

  • Research Products

    (14 results)

All Other

All Publications (14 results)

  • [Publications] Yamada M, Yagita H, Inoue H et al.: "Selective accumulation of CCR4+ T lymphocytes into renal tissue of patients with lupus nephritis."Arthritis & Rheumatism. 46(3). 735-740 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Funauchi M, Ikoma S, Enomoto H, Horiuchi A.: "Decreased Th1-1ike and increased Th2-like cells in systemic lupus erythematosus."Scand J Rheumatol. 27. 219-24 (1998)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Akahoshi,M, Nakashima,H, Tanaka,Y, et al.: "Th1/Th2 balance of peripheral T helper cells in systemic lupus erythematosus"Arthritis Rheum. 42. 1644-1648 (1999)

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  • [Publications] Klinman,DM, Steinberg,AD: "Inquiry into murine and human lupus"Immunol Rev. 144. 157-193 (1995)

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  • [Publications] Bonecchi R, Bianchi G, Bordignon PP, et al.: "Differential expression of chemokine receptors and chemotactic responsiveness of type IT helper cells (This) and Th2s."J Exp Med. 187. 129-134 (1998)

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  • [Publications] Sallusto,F, Mackay,CR, Lanzavecchia,A: "Selective expression of the eotaxin receptor CCR3 by human T helper 2 cells"Science. 277. 2005-2007 (1997)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Imai,T, Nagira,M, Takagi,S et al.: "Selective recruitment of CCR4-bearing Th2 cells toward antigen- presenting cells by the CC chemokines thymus and activation-regulated chemokine and macrophage-derived chemokine."Int Inununol. 11. 81-88 (1999)

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  • [Publications] Zingoni,A, Soto,H, Hedrick,JA, et al.: "The chemokine receptor CCR8 is preferentially expressed in Th2 but not Thl cells."J Immunol. 161. 547-551 (1998)

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  • [Publications] Loetscher P, Uguccioni M, Bordoli L., et al.: "CCR5 is characteristic of Thl lymphocytes [letter]."Nature. 391. 344-345 (1998)

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  • [Publications] Qin,S, Rottman,JB, Myers,P, et al.: "The chemokine receptors CXCR3 and CCR5 mark subsets of T cells associated with certain inflammatory reactions."J Clin Invest. 101. 746-754 (1998)

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  • [Publications] Tan,EM, Cohbn,AS, Fries,JF et al.: "The 1982 revised criteria for the classification of systemic lupus erythematosus."Arthritis Rheum. 25. 1271-1277 (1982)

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  • [Publications] Bombardier,C, Gladman,DD, Urowitz,MB, Caron,D, Chang,CH: "Derivation of the SLEDAI. A disease activity index for lupus patients. The Committee on Prognosis Studies in SLE."Arthritis Rheum. 35. 630-640 (1992)

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  • [Publications] Suzuki,N, Nakajima,A, Yoshino,S, Matsushima,K, Yagita,H, Okumura,K: "Selective accumulation of CCR5^+ T lymphocytes into inflamed joints of rheumatoid arthritis."Int Immunol. 11. 553-559 (1999)

    • Description
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  • [Publications] D'Ambrosio,D, Iellem,A, Bonecchi,R et al.: "Selective up-regulation of chemokine receptors CCR4 and CCR8 upon activation of polarized human type 2 Th cells."J Immunol. 161. 5111-5115 (1998)

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Published: 2004-04-14  

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