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Enhanced Engagement of CTLA-4 Induces Antigen-Specific CD4+CD25+Foxp3+ and CD4+CD25− TGF-β1+ Adaptive Regulatory T Cells
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| Zeitschriftentitel: | The Journal of Immunology |
|---|---|
| Personen und Körperschaften: | , , , , , |
| In: | The Journal of Immunology, 179, 2007, 8, S. 5191-5203 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
The American Association of Immunologists
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| Schlagwörter: |
| author_facet |
Li, Ruobing Perez, Nicolas Karumuthil-Melethil, Subha Prabhakar, Bellur S. Holterman, Mark J. Vasu, Chenthamarakshan Li, Ruobing Perez, Nicolas Karumuthil-Melethil, Subha Prabhakar, Bellur S. Holterman, Mark J. Vasu, Chenthamarakshan |
|---|---|
| author |
Li, Ruobing Perez, Nicolas Karumuthil-Melethil, Subha Prabhakar, Bellur S. Holterman, Mark J. Vasu, Chenthamarakshan |
| spellingShingle |
Li, Ruobing Perez, Nicolas Karumuthil-Melethil, Subha Prabhakar, Bellur S. Holterman, Mark J. Vasu, Chenthamarakshan The Journal of Immunology Enhanced Engagement of CTLA-4 Induces Antigen-Specific CD4+CD25+Foxp3+ and CD4+CD25− TGF-β1+ Adaptive Regulatory T Cells Immunology Immunology and Allergy |
| author_sort |
li, ruobing |
| spelling |
Li, Ruobing Perez, Nicolas Karumuthil-Melethil, Subha Prabhakar, Bellur S. Holterman, Mark J. Vasu, Chenthamarakshan 0022-1767 1550-6606 The American Association of Immunologists Immunology Immunology and Allergy http://dx.doi.org/10.4049/jimmunol.179.8.5191 <jats:title>Abstract</jats:title> <jats:p>CTLA-4 is a critical negative regulator of T cell response and is instrumental in maintaining immunological tolerance. In this article, we report that enhanced selective engagement of CTLA-4 on T cells by Ag-presenting dendritic cells resulted in the induction of Ag-specific CD4+CD25+Foxp3+ and CD4+CD25−TGF-β1+ adaptive Tregs. These cells were CD62Llow and hyporesponsive to stimulation with cognate Ag but demonstrated a superior ability to suppress Ag-specific effector T cell response compared with their CD62Lhigh counterparts. Importantly, treatment of mice with autoimmune thyroiditis using mouse thyroglobulin (mTg)-pulsed anti-CTLA-4 agonistic Ab-coated DCs, which results in a dominant engagement of CTLA-4 upon self-Ag presentation, not only suppressed thyroiditis but also prevented reemergence of the disease upon rechallenge with mTg. Further, the disease suppression was associated with significantly reduced mTg-specific T cell and Ab responses. Collectively, our results showed an important role for selective CTLA-4 signaling in the induction of adaptive Tregs and suggested that approaches that allow dominant CTLA-4 engagement concomitant with Ag-specific TCR ligation can be used for targeted therapy.</jats:p> Enhanced Engagement of CTLA-4 Induces Antigen-Specific CD4+CD25+Foxp3+ and CD4+CD25− TGF-β1+ Adaptive Regulatory T Cells The Journal of Immunology |
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The American Association of Immunologists, 2007 |
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The American Association of Immunologists, 2007 |
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| title |
Enhanced Engagement of CTLA-4 Induces Antigen-Specific CD4+CD25+Foxp3+ and CD4+CD25− TGF-β1+ Adaptive Regulatory T Cells |
| title_unstemmed |
Enhanced Engagement of CTLA-4 Induces Antigen-Specific CD4+CD25+Foxp3+ and CD4+CD25− TGF-β1+ Adaptive Regulatory T Cells |
| title_full |
Enhanced Engagement of CTLA-4 Induces Antigen-Specific CD4+CD25+Foxp3+ and CD4+CD25− TGF-β1+ Adaptive Regulatory T Cells |
| title_fullStr |
Enhanced Engagement of CTLA-4 Induces Antigen-Specific CD4+CD25+Foxp3+ and CD4+CD25− TGF-β1+ Adaptive Regulatory T Cells |
| title_full_unstemmed |
Enhanced Engagement of CTLA-4 Induces Antigen-Specific CD4+CD25+Foxp3+ and CD4+CD25− TGF-β1+ Adaptive Regulatory T Cells |
| title_short |
Enhanced Engagement of CTLA-4 Induces Antigen-Specific CD4+CD25+Foxp3+ and CD4+CD25− TGF-β1+ Adaptive Regulatory T Cells |
| title_sort |
enhanced engagement of ctla-4 induces antigen-specific cd4+cd25+foxp3+ and cd4+cd25− tgf-β1+ adaptive regulatory t cells |
| topic |
Immunology Immunology and Allergy |
| url |
http://dx.doi.org/10.4049/jimmunol.179.8.5191 |
| publishDate |
2007 |
| physical |
5191-5203 |
| description |
<jats:title>Abstract</jats:title>
<jats:p>CTLA-4 is a critical negative regulator of T cell response and is instrumental in maintaining immunological tolerance. In this article, we report that enhanced selective engagement of CTLA-4 on T cells by Ag-presenting dendritic cells resulted in the induction of Ag-specific CD4+CD25+Foxp3+ and CD4+CD25−TGF-β1+ adaptive Tregs. These cells were CD62Llow and hyporesponsive to stimulation with cognate Ag but demonstrated a superior ability to suppress Ag-specific effector T cell response compared with their CD62Lhigh counterparts. Importantly, treatment of mice with autoimmune thyroiditis using mouse thyroglobulin (mTg)-pulsed anti-CTLA-4 agonistic Ab-coated DCs, which results in a dominant engagement of CTLA-4 upon self-Ag presentation, not only suppressed thyroiditis but also prevented reemergence of the disease upon rechallenge with mTg. Further, the disease suppression was associated with significantly reduced mTg-specific T cell and Ab responses. Collectively, our results showed an important role for selective CTLA-4 signaling in the induction of adaptive Tregs and suggested that approaches that allow dominant CTLA-4 engagement concomitant with Ag-specific TCR ligation can be used for targeted therapy.</jats:p> |
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| author | Li, Ruobing, Perez, Nicolas, Karumuthil-Melethil, Subha, Prabhakar, Bellur S., Holterman, Mark J., Vasu, Chenthamarakshan |
| author_facet | Li, Ruobing, Perez, Nicolas, Karumuthil-Melethil, Subha, Prabhakar, Bellur S., Holterman, Mark J., Vasu, Chenthamarakshan, Li, Ruobing, Perez, Nicolas, Karumuthil-Melethil, Subha, Prabhakar, Bellur S., Holterman, Mark J., Vasu, Chenthamarakshan |
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| description | <jats:title>Abstract</jats:title> <jats:p>CTLA-4 is a critical negative regulator of T cell response and is instrumental in maintaining immunological tolerance. In this article, we report that enhanced selective engagement of CTLA-4 on T cells by Ag-presenting dendritic cells resulted in the induction of Ag-specific CD4+CD25+Foxp3+ and CD4+CD25−TGF-β1+ adaptive Tregs. These cells were CD62Llow and hyporesponsive to stimulation with cognate Ag but demonstrated a superior ability to suppress Ag-specific effector T cell response compared with their CD62Lhigh counterparts. Importantly, treatment of mice with autoimmune thyroiditis using mouse thyroglobulin (mTg)-pulsed anti-CTLA-4 agonistic Ab-coated DCs, which results in a dominant engagement of CTLA-4 upon self-Ag presentation, not only suppressed thyroiditis but also prevented reemergence of the disease upon rechallenge with mTg. Further, the disease suppression was associated with significantly reduced mTg-specific T cell and Ab responses. Collectively, our results showed an important role for selective CTLA-4 signaling in the induction of adaptive Tregs and suggested that approaches that allow dominant CTLA-4 engagement concomitant with Ag-specific TCR ligation can be used for targeted therapy.</jats:p> |
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| imprint | The American Association of Immunologists, 2007 |
| imprint_str_mv | The American Association of Immunologists, 2007 |
| institution | DE-Pl11, DE-Rs1, DE-105, DE-14, DE-Ch1, DE-L229, DE-D275, DE-Bn3, DE-Brt1, DE-Zwi2, DE-D161, DE-Gla1, DE-Zi4, DE-15 |
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| spelling | Li, Ruobing Perez, Nicolas Karumuthil-Melethil, Subha Prabhakar, Bellur S. Holterman, Mark J. Vasu, Chenthamarakshan 0022-1767 1550-6606 The American Association of Immunologists Immunology Immunology and Allergy http://dx.doi.org/10.4049/jimmunol.179.8.5191 <jats:title>Abstract</jats:title> <jats:p>CTLA-4 is a critical negative regulator of T cell response and is instrumental in maintaining immunological tolerance. In this article, we report that enhanced selective engagement of CTLA-4 on T cells by Ag-presenting dendritic cells resulted in the induction of Ag-specific CD4+CD25+Foxp3+ and CD4+CD25−TGF-β1+ adaptive Tregs. These cells were CD62Llow and hyporesponsive to stimulation with cognate Ag but demonstrated a superior ability to suppress Ag-specific effector T cell response compared with their CD62Lhigh counterparts. Importantly, treatment of mice with autoimmune thyroiditis using mouse thyroglobulin (mTg)-pulsed anti-CTLA-4 agonistic Ab-coated DCs, which results in a dominant engagement of CTLA-4 upon self-Ag presentation, not only suppressed thyroiditis but also prevented reemergence of the disease upon rechallenge with mTg. Further, the disease suppression was associated with significantly reduced mTg-specific T cell and Ab responses. Collectively, our results showed an important role for selective CTLA-4 signaling in the induction of adaptive Tregs and suggested that approaches that allow dominant CTLA-4 engagement concomitant with Ag-specific TCR ligation can be used for targeted therapy.</jats:p> Enhanced Engagement of CTLA-4 Induces Antigen-Specific CD4+CD25+Foxp3+ and CD4+CD25− TGF-β1+ Adaptive Regulatory T Cells The Journal of Immunology |
| spellingShingle | Li, Ruobing, Perez, Nicolas, Karumuthil-Melethil, Subha, Prabhakar, Bellur S., Holterman, Mark J., Vasu, Chenthamarakshan, The Journal of Immunology, Enhanced Engagement of CTLA-4 Induces Antigen-Specific CD4+CD25+Foxp3+ and CD4+CD25− TGF-β1+ Adaptive Regulatory T Cells, Immunology, Immunology and Allergy |
| title | Enhanced Engagement of CTLA-4 Induces Antigen-Specific CD4+CD25+Foxp3+ and CD4+CD25− TGF-β1+ Adaptive Regulatory T Cells |
| title_full | Enhanced Engagement of CTLA-4 Induces Antigen-Specific CD4+CD25+Foxp3+ and CD4+CD25− TGF-β1+ Adaptive Regulatory T Cells |
| title_fullStr | Enhanced Engagement of CTLA-4 Induces Antigen-Specific CD4+CD25+Foxp3+ and CD4+CD25− TGF-β1+ Adaptive Regulatory T Cells |
| title_full_unstemmed | Enhanced Engagement of CTLA-4 Induces Antigen-Specific CD4+CD25+Foxp3+ and CD4+CD25− TGF-β1+ Adaptive Regulatory T Cells |
| title_short | Enhanced Engagement of CTLA-4 Induces Antigen-Specific CD4+CD25+Foxp3+ and CD4+CD25− TGF-β1+ Adaptive Regulatory T Cells |
| title_sort | enhanced engagement of ctla-4 induces antigen-specific cd4+cd25+foxp3+ and cd4+cd25− tgf-β1+ adaptive regulatory t cells |
| title_unstemmed | Enhanced Engagement of CTLA-4 Induces Antigen-Specific CD4+CD25+Foxp3+ and CD4+CD25− TGF-β1+ Adaptive Regulatory T Cells |
| topic | Immunology, Immunology and Allergy |
| url | http://dx.doi.org/10.4049/jimmunol.179.8.5191 |