1. Volume 131, Issue 2, Pages 606-618 (August 2006)
Autoreactive T-Cell Responses in Primary Biliary Cirrhosis Are Proinflammatory Whereas Those of Controls Are Regulatory 
Shinji Shimoda, Fumihiko Ishikawa, Takashi Kamihira, Atsumasa Komori, Hiroaki Niiro, Eishi Baba, Kenichi Harada, Kumiko Isse, Yasuni Nakanuma, Hiromi Ishibashi, M. Eric Gershwin, Mine Harada 
Gastroenterology 
Volume 131, Issue 2, Pages (August 2006)
DOI: /j.gastro
Copyright © 2006 American Gastroenterological Association Institute Terms and Conditions

2. Figure 1
ELISPOT assay (IFN-γ, IL-10, and IL-4) of patients with PBC and controls. Cytokine production of T cells in response to PDC-E2 163–176 peptide using irradiated autologous PBMCs or MMC-treated L-DR53 cells as APCs using ELISPOT. The y-axis indicates the number of cytokine-producing T cells reactive to PDC-E2 163–176 peptide/3 × 105 PBMCs. Note that, in controls, there is a significant decrease in IFN-γ production (P < .01) and maintenance of IL-10 production (P = .28) using L-DR53 cells compared with PBMCs. Open circles, PBC; closed circles, controls. The median line within the box is the average and includes ±SEM.
Gastroenterology  , DOI: ( /j.gastro )
Copyright © 2006 American Gastroenterological Association Institute Terms and Conditions

3. Figure 2
The proliferation and cytokine production of a costimulation-dependent TCC (TCC dependent 1 from control 5) using PBMCs and L-DR53 cells as APCs. The TCC was cocultured with Ag-pulsed or control PBMCs or L-DR53 cells as APCs. It proliferated and produced both IFN-γ and IL-10 when cocultured with Ag-pulsed PBMCs. It did not proliferate and did not produce IFN-γ but secreted IL-10 when cocultured with Ag-pulsed L-DR53 cells. The TCC essentially did not produce IL-4 when cocultured with Ag-pulsed PBMCs or L-DR53 cells.
Gastroenterology  , DOI: ( /j.gastro )
Copyright © 2006 American Gastroenterological Association Institute Terms and Conditions

4. Figure 3
The proliferation and cytokine production of a costimulation-independent TCC (TCC independent 1) using PBMCs and L-DR53 cells as APCs. The TCC was cocultured with Ag-pulsed or control PBMCs or L-DR53 cells as APCs. When cocultured with Ag-pulsed PBMCs or L-DR53 cells, the TCC proliferated and produced IFN-γ and IL-10 but not IL-4.
Gastroenterology  , DOI: ( /j.gastro )
Copyright © 2006 American Gastroenterological Association Institute Terms and Conditions

5. Figure 4
The proliferation and cytokine production of an L(1) state of costimulation-dependent TCC (TCC dependent 1). The L(1) state of TCCs did not proliferate or did not produce IFN-γ but produced IL-10 with Ag-pulsed PBMCs or L-DR53 cells as APCs. TCC dependent 1 was rendered anergic after a single round of stimulation with Ag-pulsed L-DR53 cells.
Gastroenterology  , DOI: ( /j.gastro )
Copyright © 2006 American Gastroenterological Association Institute Terms and Conditions

6. Figure 5
The proliferation and cytokine production of an L(1) or L(2) state of complete costimulation-independent TCC (TCC independent 4). The L(1) state of TCC proliferated and produced IFN-γ and IL-10 with Ag-pulsed PBMCs or L-DR53 cells as APCs. The L(2) state of TCC proliferated and produced IFN-γ and IL-10 with Ag-pulsed PBMCs or L-DR53 cells as APCs. The TCC independent 4 was not rendered anergic by a single round of stimulation with Ag-pulsed L-DR53 cells (L(1) stage) or after the second stimulation with Ag-pulsed L-DR53 cells (L(2) stage).
Gastroenterology  , DOI: ( /j.gastro )
Copyright © 2006 American Gastroenterological Association Institute Terms and Conditions

7. Figure 6
The proliferation and cytokine production of an L(1) or L(2) state of costimulation relative independent TCC (TCC independent 1). The L(1) state of TCCs proliferated and produced IFN-γ and IL-10 with Ag-pulsed PBMCs or L-DR53 cells as APCs. The L(2) state of TCCs did not proliferate or did not produce IFN-γ but produced IL-10 with Ag-pulsed PBMC or L-DR53 cells as APCs. The TCC independent 1 was not rendered anergic by a single round of stimulation with Ag-pulsed L-DR53 cells (L(1) stage) but became anergic after the second stimulation with Ag-pulsed L-DR53 cells (L(2) stage).
Gastroenterology  , DOI: ( /j.gastro )
Copyright © 2006 American Gastroenterological Association Institute Terms and Conditions

8. Figure 7
Regulatory function of anergic T cells. (A) L(1) state of TCC dependent 1, which is anergic, was added to the proliferation assays of the corresponding TCC. The proliferation of TCC dependent 1 was regulated when anergic L(1) TCC was added. (B) L(1) state of TCC relative independent 1, which is not anergic, or L(2) state of TCC relative independent 1, which is anergic, was added to the proliferation assays of the corresponding TCC. The proliferation of TCC relative independent 1 was not regulated when nonanergic TCC was added but the proliferation of TCC was regulated when anergic TCC was added. (C) L(1) state of TCC complete independent 4, which is not anergic, or L(2) state of TCC complete independent 4, which is not anergic, was added to the proliferation assays of the corresponding TCC. The proliferation of TCCs was not regulated when nonanergic L(1) state of the corresponding TCC or nonanergic L(2) state of the corresponding TCC was added. Only anergic T cells regulated the proliferation of TCCs.
Gastroenterology  , DOI: ( /j.gastro )
Copyright © 2006 American Gastroenterological Association Institute Terms and Conditions

9. Figure 8
Cellular interaction of anergic T cells is not required for regulatory functions. L(1) state of TCC dependent 1, which is anergic, or irradiated L(1) state of TCC (3000 rad) was added directly to the proliferation assay of the same TCC dependent 1. The proliferation of TCCs was regulated when nonirradiated L(1) state of TCCs was added but not regulated when irradiated L(1) state of TCCs was added.
Gastroenterology  , DOI: ( /j.gastro )
Copyright © 2006 American Gastroenterological Association Institute Terms and Conditions

10. Figure 9
The regulatory function of anergic T cells is partially due to IL-10. The proliferation of TCC dependent 1 was regulated when anergic L(1) state of TCCs or supernatant of anergic L(1) state of TCCs was added and partially recovered when anti–IL-10 antibody was added. Anergic T cells or their cell-free supernatants regulate the Ag-specific proliferation of T cells. Note the partial abrogation of the suppressor activity exerted by anergic T cells in the presence of anti–IL-10 monoclonal antibody.
Gastroenterology  , DOI: ( /j.gastro )
Copyright © 2006 American Gastroenterological Association Institute Terms and Conditions

11. Figure 10
Regulatory functions of anergic T cells are Ag dependent. The proliferation of TCCs that respond to PPD was not regulated when anergic L(1) state of TCCs, which respond to PDC-E2 163–176, was added in the absence of PDC-E2 163–176 but was regulated when anergic L(1) state of TCCs, which respond to PDC-E2 163–176, was added in the presence of PDC-E2 163–176. The restoration of suppressor activity by the addition of PDC-E2 163–176 indicates that the regulatory function of anergic TCCs requires the presence of Ag.
Gastroenterology  , DOI: ( /j.gastro )
Copyright © 2006 American Gastroenterological Association Institute Terms and Conditions