1995 Fiscal Year Annual Research Report

インターロイキン2(IL-2)の作用を標的とした免疫抑制剤の開発

Research Project

Project/Area Number	05557022
Research Institution	TOHOKU UNIVERSITY
Principal Investigator	菅村和夫東北大学, 医学部, 教授 (20117360)
Co-Investigator(Kenkyū-buntansha)	里見進東北大学, 医学部, 教授 (00154120) 佐々木毅東北大学, 医学部, 教授 (50110656) 浅尾裕信東北大学, 医学部, 助手 (80250744)
Keywords	免疫抑制 / IL-2受容体 / 単クロン抗体 / 移植免疫
Research Abstract	移植拒絶反応の治療や自己免疫疾患の治療には副作用の少ない免疫抑制剤が有用である。本研究では免疫系を支えるIL-2の作用を特異的に抑制する方法の確立を試みる。本年度はマウスの皮膚移植系およびMixed lymphocyte reaction(MLR)、CTLアッセイを用いて、IL-2受容体α鎖、β鎖、γ鎖のそれぞれに対する単クロン抗体の投与による移植免疫抑制作用を詳細に解析した。その結果、まずCBA/N(H-2^k),BALB/C(H-2^d)マウス脾細胞間のMLRにおいて抗α鎖、抗β鎖あるいは抗γ鎖抗体単独投与によりそれぞれ約50%の抑制がみられ、3者併用により70%の抑制が認められた。次に、CBA/N,BALB/Cマウスをそれぞれレシピエント、ドナーとして皮膚移植を行った。その結果、対照群で平均6日であった生着期間が抗α鎖および抗β鎖抗体投与により11日に延長し、抗γ鎖を加えた3者併用により22日へと著名な生着延長が認められた。さらに、CBA/NにBALB/C由来脾細胞を免疫後、p815(H-2^d)を標的としてCTLアッセイを行った結果、抗α、抗β鎖抗体2者併用により約50%の抑制がみられ、抗γ鎖抗体を加えた3者併用によりほぼ完全な抑制が認められた。

Research Products
(15 results)

All Other

All Publications (15 results)

[Publications] Ishii,N.: "mAb specific for the γ chain of the IL-2 receptor." Leucocyte Typing V. 2. 1867-1868 (1995)
[Publications] Kimura,Y.: "Sharing of the IL-2 receptor γ chain with the functional IL-9 receptor complex." Inter.Immunol.7. 115-120 (1995)
[Publications] Watanabe,S.: "Involvement of the IL-2 receptor γ subunit in IL-4-dependent activation of mouse hematopoietic cells and splenic B cells." Eur.J.Immunol.25. 126-131 (1995)
[Publications] Ohbo,K.: "Functional analysis of the human interleukin 2 receptor γ chain gene promoter." J.Biol.Chem.270. 7479-7486 (1995)
[Publications] Sugamura,K.: "The common γ chain for multiple cytokine receptors." Adv.Immunol.59. 225-277 (1995)
[Publications] Moreau,J.L.: "Control by interleukin-2 and interleukin-4 of the IL-2 responsiveness of murine B cells." J.Immunol.155. 3401-3408 (1995)
[Publications] Kumaki,S.: "Characterization of B cell lines established from two X-linked severe combined immunodificiency patients:interleukin-15 binds to the B cells but not internalized efficiently." Blood. 86. 1428-1436 (1995)
[Publications] Nemoto,T.: "Difference in interleukin 2(IL-2)receptor system between human and mouse:essential requirement of the α chain for formation of the functional mouse IL-2 receptor." Eur.J.Immunol.25. 3001-3005 (1995)
[Publications] Clark,C.J.P.: "Interleukin 4 inhibits κ light chain expression and NFκB activation but not IkBa degradation in 70Z/3 murine pre-B cells." Eur.J.Immunol. 25. 2961-2966 (1995)
[Publications] Edelbaum,D.,: "Interleukin(IL)-15 promotes the growth of murine epidermal γδ T cells by a mechanism involving the β-and γc-chains of the IL-2 receptor." J.Invest.Dermatol.105. 837-843 (1995)
[Publications] Ohbo,K.: "Modulation of hematopoiesis in mouse with a truncated mutant of the interleukin-2 receptor γ chain." Blood. 87. 956-967 (1996)
[Publications] Sugamura,K.: "The interleukin 2 receptor γ chain:its role in the multiple cytokine receptor complexes and T cell development in XSCID." Annu.Rev.Immunol.14. 179-205 (1996)
[Publications] Saito,S.: "Expression of the interleukin-2 receptor (IL-2R)γ chain on cord blood mononuclear cells." Blood. (in press.).
[Publications] Schnyder,B.: "IL-4 and IL-13 bind to a shared heterodimeric complex on endothelial cells mediating vascular cell adhesion molecule-1 induction in the absence of the common γ chain(γc)." Blood. (in press.).
[Publications] Ohbo,K.: "Demonstration of a crosstalk between IL-2 and IL-5 in phosphorylation of IL-2 and IL-5 receptor β chains." Inter.Immunol.(in press.).

1995 Fiscal Year Annual Research Report

インターロイキン2(IL-2)の作用を標的とした免疫抑制剤の開発

Principal Investigator

菅村 和夫 東北大学, 医学部, 教授 (20117360)

Research Products

[Publications] Ishii,N.: "mAb specific for the γ chain of the IL-2 receptor." Leucocyte Typing V. 2. 1867-1868 (1995)

[Publications] Kimura,Y.: "Sharing of the IL-2 receptor γ chain with the functional IL-9 receptor complex." Inter.Immunol.7. 115-120 (1995)

[Publications] Watanabe,S.: "Involvement of the IL-2 receptor γ subunit in IL-4-dependent activation of mouse hematopoietic cells and splenic B cells." Eur.J.Immunol.25. 126-131 (1995)

[Publications] Ohbo,K.: "Functional analysis of the human interleukin 2 receptor γ chain gene promoter." J.Biol.Chem.270. 7479-7486 (1995)

[Publications] Sugamura,K.: "The common γ chain for multiple cytokine receptors." Adv.Immunol.59. 225-277 (1995)

[Publications] Moreau,J.L.: "Control by interleukin-2 and interleukin-4 of the IL-2 responsiveness of murine B cells." J.Immunol.155. 3401-3408 (1995)

[Publications] Kumaki,S.: "Characterization of B cell lines established from two X-linked severe combined immunodificiency patients:interleukin-15 binds to the B cells but not internalized efficiently." Blood. 86. 1428-1436 (1995)

[Publications] Nemoto,T.: "Difference in interleukin 2(IL-2)receptor system between human and mouse:essential requirement of the α chain for formation of the functional mouse IL-2 receptor." Eur.J.Immunol.25. 3001-3005 (1995)

[Publications] Clark,C.J.P.: "Interleukin 4 inhibits κ light chain expression and NFκB activation but not IkBa degradation in 70Z/3 murine pre-B cells." Eur.J.Immunol. 25. 2961-2966 (1995)

[Publications] Edelbaum,D.,: "Interleukin(IL)-15 promotes the growth of murine epidermal γδ T cells by a mechanism involving the β-and γc-chains of the IL-2 receptor." J.Invest.Dermatol.105. 837-843 (1995)

[Publications] Ohbo,K.: "Modulation of hematopoiesis in mouse with a truncated mutant of the interleukin-2 receptor γ chain." Blood. 87. 956-967 (1996)

[Publications] Sugamura,K.: "The interleukin 2 receptor γ chain:its role in the multiple cytokine receptor complexes and T cell development in XSCID." Annu.Rev.Immunol.14. 179-205 (1996)

[Publications] Saito,S.: "Expression of the interleukin-2 receptor (IL-2R)γ chain on cord blood mononuclear cells." Blood. (in press.).

[Publications] Schnyder,B.: "IL-4 and IL-13 bind to a shared heterodimeric complex on endothelial cells mediating vascular cell adhesion molecule-1 induction in the absence of the common γ chain(γc)." Blood. (in press.).

[Publications] Ohbo,K.: "Demonstration of a crosstalk between IL-2 and IL-5 in phosphorylation of IL-2 and IL-5 receptor β chains." Inter.Immunol.(in press.).

菅村和夫東北大学, 医学部, 教授 (20117360)