1997 Fiscal Year Annual Research Report

遺伝子ノックアウトマウスを用いた細菌初期感染防御機構の分子基盤の解析

Research Project

Project/Area Number	09470076
Research Institution	Nagoya University
Principal Investigator	吉開泰信名古屋大学, 医学部, 教授 (90158402)
Co-Investigator(Kenkyū-buntansha)	西村仁志名古屋大学, 医学部, 助手 (00283440)
Keywords	マウスサルモネラ感染症 / γδ型T細胞 / β2ミクログロブリンノックアウトマウス / MHCクラスIIノックアウトマウス
Research Abstract	γδ型T細胞は、個体の発生早期に出現し、表皮や腸管などの上皮間に多く存在するユニークなTリンパ球である。その機能としては感染の初期防御機構として働くことが報告されている。我々はγδ型T細胞の感染防御における役割を明らかにする目的でγδ型T細胞の抗原認識機構について遺伝子ノックアウトマウスを用いて解析した。 C57BL/6マウスにSalmonella choleraesuisを腹腔内に投与して6日目の腹腔内滲出Tリンパ球から抗TCRγδ抗体を用いたpositive panning法にて95%以上に純化したγδ型T細胞を回収し、さらにNK1.1陽性T細胞をセルソーターによってソーティングしてvγ/δレパートア-及びサイトカインmRNAをRT-PCR法で調べた。その結果、NK1.1陽性γδ型T細胞はVγ4/Vδ4を主に発現した。次に、γδ型T細胞の反応系を^3-サイミジンの取り込み反応及びサイトカイン産生能で検討した。ソーティングしたNK1.1陽性γδ型T細胞はPHA刺激脾細胞を用いたときに自己反応性を示した。抗原提示細胞にMHCクラスII (IAβ)ノックアウトマウスまたはMHCクラスI(β2ミクログロブリン)ノックアウトマウス由来の脾細胞を用いたところ、IAβノックアウトマウス由来の抗原提示細胞に対するNK1.1陽性γδ型T細胞の自己反応性は認められなかった。NK1.1陽性γδ型T細胞は、wildタイプのIA^bまたはIEa52-68ペプチドをcovalentに結合した変異IA^b発現細胞にも反応した。この結果よりNK1.1陽性γδ型T細胞はMHCクラスII分子(IA)をその結合ペプチドとは非依存的に認識すると考えられる。

Research Products
(17 results)

All Other

All Publications (17 results)

[Publications] Enomoto,A.: "Predominant appearance of NK1.1^+ T cells producing IL-4 in the peritoneal cavity of mice with beige mutation during Salmonella infection." J.Immunol.158. 2268-2277 (1997)
[Publications] Sakai, T.: "Fas-mediated cytotoxicity by host intestinal intraepithelial lymphocytes is involved in the enteropathy during acute graft-vs.-host disease." Gastroenterology. 113. 168-174 (1997)
[Publications] Nishimura, H.: "Hsp 70 protects macrophages infected with Salmonella choleraesuis against TNFα-induced cell death." Cell Stress & Chaperones. 2. 50-59 (1997)
[Publications] Kobayashi, Y.: "Aggravation of murine experimental allergic encephalitis by T cell receptor γδ-specific antibody." J.Neuroimmunol.73. 169-174 (1997)
[Publications] Fuse, Y.: "CD95 (Fas) may control the expansion of activated T cells after elimination of bacteria during the course of murine listeriosis." Infect.Immun.65. 1883-1891 (1997)
[Publications] Kakumu, S.: "Serum levels of IL-10, IL-15, and soluble tumor necrosis factor-α receptors in type C chronic liver disease." Clin.Exp.Immunol.109. 458-463 (1997)
[Publications] Inagaki-Ohara, K.: "Interleukin-15 preferentially promotes the growth of intestinal intrapithelial lymphocytes bearing γδ T cell receptor in mice." Eur.J.Immunol.27. 2885-2891 (1997)
[Publications] Inagaki-Ohara, K.: "Involvement of fas antigen/fas ligand interaction in apoptosis of epithelial cells by intraepithelial lymphocytes in murine small intestine." Lab.Invest.77. 421-429 (1997)
[Publications] Ito,K.: "Murine model of IgE produdtion with a predominant Th2-response by feeding protein antigen without adjuvants." Eur.J.Immunol.27. 3427-3437 (1997)
[Publications] Kobayashi, N.: "A sustained increase of cytosolic Ca^<2+> may be responsible for apoptosis in γδ T cells triggered by co-stimulation via TCR/CD3 and LFA-1." Cell Calcium.22. 421-430 (1997)
[Publications] Nishimura, H.: "Translational efficiency is upregulated by alternative exon in murine interleukin-15 mRNA." J.Immunol.160. 936-942 (1998)
[Publications] Kimura, Y.: "The regulatory role of heat shock protein 70-reactive CD4^+ T cells during rat listeriosis." Int.Immunol.(in press). (1998)
[Publications] Sakai, T.: "Interleukin 15 activity in the intestinal mucosa of inflammatory bowel disease." Gastroenterology. (in press). (1998)
[Publications] Washizu, J.: "NF-κB binding site is essential for transcriptional activation of IL-15." Immunogenetics. (in press). (1998)
[Publications] Takano, M.: "A protective role of Il-15-dependent γδ T cells in Escherichia coli infection in mice." Infect.Immun.(in press). (1998)
[Publications] 吉開泰信: "γδT細胞の多形性" アレルギー科. 4 (5). 445-453 (1997)
[Publications] 吉開泰信: "γδT細胞と細菌感染" 実験医学. 15 (11). 196-201 (1997)

1997 Fiscal Year Annual Research Report

遺伝子ノックアウトマウスを用いた細菌初期感染防御機構の分子基盤の解析

Principal Investigator

吉開 泰信 名古屋大学, 医学部, 教授 (90158402)

Research Products

[Publications] Enomoto,A.: "Predominant appearance of NK1.1^+ T cells producing IL-4 in the peritoneal cavity of mice with beige mutation during Salmonella infection." J.Immunol.158. 2268-2277 (1997)

[Publications] Sakai, T.: "Fas-mediated cytotoxicity by host intestinal intraepithelial lymphocytes is involved in the enteropathy during acute graft-vs.-host disease." Gastroenterology. 113. 168-174 (1997)

[Publications] Nishimura, H.: "Hsp 70 protects macrophages infected with Salmonella choleraesuis against TNFα-induced cell death." Cell Stress & Chaperones. 2. 50-59 (1997)

[Publications] Kobayashi, Y.: "Aggravation of murine experimental allergic encephalitis by T cell receptor γδ-specific antibody." J.Neuroimmunol.73. 169-174 (1997)

[Publications] Fuse, Y.: "CD95 (Fas) may control the expansion of activated T cells after elimination of bacteria during the course of murine listeriosis." Infect.Immun.65. 1883-1891 (1997)

[Publications] Kakumu, S.: "Serum levels of IL-10, IL-15, and soluble tumor necrosis factor-α receptors in type C chronic liver disease." Clin.Exp.Immunol.109. 458-463 (1997)

[Publications] Inagaki-Ohara, K.: "Interleukin-15 preferentially promotes the growth of intestinal intrapithelial lymphocytes bearing γδ T cell receptor in mice." Eur.J.Immunol.27. 2885-2891 (1997)

[Publications] Inagaki-Ohara, K.: "Involvement of fas antigen/fas ligand interaction in apoptosis of epithelial cells by intraepithelial lymphocytes in murine small intestine." Lab.Invest.77. 421-429 (1997)

[Publications] Ito,K.: "Murine model of IgE produdtion with a predominant Th2-response by feeding protein antigen without adjuvants." Eur.J.Immunol.27. 3427-3437 (1997)

[Publications] Kobayashi, N.: "A sustained increase of cytosolic Ca^<2+> may be responsible for apoptosis in γδ T cells triggered by co-stimulation via TCR/CD3 and LFA-1." Cell Calcium.22. 421-430 (1997)

[Publications] Nishimura, H.: "Translational efficiency is upregulated by alternative exon in murine interleukin-15 mRNA." J.Immunol.160. 936-942 (1998)

[Publications] Kimura, Y.: "The regulatory role of heat shock protein 70-reactive CD4^+ T cells during rat listeriosis." Int.Immunol.(in press). (1998)

[Publications] Sakai, T.: "Interleukin 15 activity in the intestinal mucosa of inflammatory bowel disease." Gastroenterology. (in press). (1998)

[Publications] Washizu, J.: "NF-κB binding site is essential for transcriptional activation of IL-15." Immunogenetics. (in press). (1998)

[Publications] Takano, M.: "A protective role of Il-15-dependent γδ T cells in Escherichia coli infection in mice." Infect.Immun.(in press). (1998)

[Publications] 吉開泰信: "γδT細胞の多形性" アレルギー科. 4 (5). 445-453 (1997)

[Publications] 吉開泰信: "γδT細胞と細菌感染" 実験医学. 15 (11). 196-201 (1997)

吉開泰信名古屋大学, 医学部, 教授 (90158402)