Activated Self-MHC-reactive T cells have the cytokine phenotype of Th3/T regulatory cell 1 T cells

Atsushi Kitani, Kevin Chua, Kazuhiko Nakamura, Warren Strober

研究成果: ジャーナルへの寄稿記事

104 引用 (Scopus)

抄録

In the present study, we show that human self-MHC-reactive (autoreactive) T cell clones are functionally distinct from Ag-specific T cell clones. Self-MHC-reactive T cells exhibited helper function for B cell Ig production when cultured with non-T cells alone, and they exhibit suppressor function when cultured with PWM- or rCD40 ligand (rCR40L)- activated non-T cells, whereas tetanus toxoid (TT)-specific clones exhibited only helper function in the presence of TT with or without PWM or rCD40L. Addition of neutralizing Abs to the cultures showed that the suppression was mediated by TGF-β but not by IL-10 or IFN-γ. The self-MHC-reactive clones also inhibited proliferation of primary CD4+ T cells and TT-specific T cell clones, but in this case the inhibition was mediated by both IL-10 and TGF- β. In further studies, the interactions between self-MHC-reactive T cell clones and non-T cells that led to suppressor cytokine production have been explored. We found that prestimulation of non-T cells for 8 h with PWM or for 48 h for rCD40L results in non-T cells capable of inducing self-MHC-reactive T cell to produce high levels of TGF-β and IL-10. In addition, these prestimulation times coincided with peak induction of HLA-DR and costimulatory B7 molecule (especially CD86) expression on B cells. Finally, addition of CTLA-4/Fc or blocking F(ab')2 anti-CTLA-4 mAb, plus optimally stimulated non-T cells, to cultures of self-MHC-reactive clones inhibited the induction of TGF-β but not IL-10 or IFN-γ production. In summary, these studies show that activated self-MHC-reactive T cells have the cytokine phenotype of Th3 or T regulatory cell 1 and thus may be important regulatory cells that mediate oral and peripheral tolerance and prevent the development of autoimmunity.

元の言語英語
ページ(範囲)691-702
ページ数12
ジャーナルJournal of Immunology
165
発行部数2
DOI
出版物ステータス出版済み - 7 15 2000

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Regulatory T-Lymphocytes
Clone Cells
Cytokines
T-Lymphocytes
Phenotype
Interleukin-10
Tetanus Toxoid
B-Lymphocytes
B7 Antigens
Peripheral Tolerance
HLA-DR Antigens
Helper-Inducer T-Lymphocytes
Autoimmunity
Cell Culture Techniques
Ligands

All Science Journal Classification (ASJC) codes

  • Immunology

これを引用

Activated Self-MHC-reactive T cells have the cytokine phenotype of Th3/T regulatory cell 1 T cells. / Kitani, Atsushi; Chua, Kevin; Nakamura, Kazuhiko; Strober, Warren.

:: Journal of Immunology, 巻 165, 番号 2, 15.07.2000, p. 691-702.

研究成果: ジャーナルへの寄稿記事

Kitani, Atsushi ; Chua, Kevin ; Nakamura, Kazuhiko ; Strober, Warren. / Activated Self-MHC-reactive T cells have the cytokine phenotype of Th3/T regulatory cell 1 T cells. :: Journal of Immunology. 2000 ; 巻 165, 番号 2. pp. 691-702.
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abstract = "In the present study, we show that human self-MHC-reactive (autoreactive) T cell clones are functionally distinct from Ag-specific T cell clones. Self-MHC-reactive T cells exhibited helper function for B cell Ig production when cultured with non-T cells alone, and they exhibit suppressor function when cultured with PWM- or rCD40 ligand (rCR40L)- activated non-T cells, whereas tetanus toxoid (TT)-specific clones exhibited only helper function in the presence of TT with or without PWM or rCD40L. Addition of neutralizing Abs to the cultures showed that the suppression was mediated by TGF-β but not by IL-10 or IFN-γ. The self-MHC-reactive clones also inhibited proliferation of primary CD4+ T cells and TT-specific T cell clones, but in this case the inhibition was mediated by both IL-10 and TGF- β. In further studies, the interactions between self-MHC-reactive T cell clones and non-T cells that led to suppressor cytokine production have been explored. We found that prestimulation of non-T cells for 8 h with PWM or for 48 h for rCD40L results in non-T cells capable of inducing self-MHC-reactive T cell to produce high levels of TGF-β and IL-10. In addition, these prestimulation times coincided with peak induction of HLA-DR and costimulatory B7 molecule (especially CD86) expression on B cells. Finally, addition of CTLA-4/Fc or blocking F(ab')2 anti-CTLA-4 mAb, plus optimally stimulated non-T cells, to cultures of self-MHC-reactive clones inhibited the induction of TGF-β but not IL-10 or IFN-γ production. In summary, these studies show that activated self-MHC-reactive T cells have the cytokine phenotype of Th3 or T regulatory cell 1 and thus may be important regulatory cells that mediate oral and peripheral tolerance and prevent the development of autoimmunity.",
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