Developing and Activated T Cell Survival Depends on Differential Signaling Pathways to Regulate Anti-Apoptotic Bcl-xL
Survival of T cells in both the central and peripheral immune system determines its ultimate function in the regulation of immune responses. In the thymus, developing T cells undergo positive and negative selection to generate a T cell repertoire that responds to foreign, but not self, antigens. Dur...
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| Format: | Article |
| Language: | English |
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Wiley
2012-01-01
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| Series: | Clinical and Developmental Immunology |
| Online Access: | http://dx.doi.org/10.1155/2012/632837 |
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| author | Ruiqing Wang Huimin Xie Zhaofeng Huang Weirong Shang Zuoming Sun |
| author_facet | Ruiqing Wang Huimin Xie Zhaofeng Huang Weirong Shang Zuoming Sun |
| author_sort | Ruiqing Wang |
| collection | DOAJ |
| description | Survival of T cells in both the central and peripheral immune system determines its ultimate function in the regulation of immune responses. In the thymus, developing T cells undergo positive and negative selection to generate a T cell repertoire that responds to foreign, but not self, antigens. During T cell development, the T cell receptor α chain is rearranged. However, the first round of rearrangement may fail, which triggers another round of α chain rearrangement until either successful positive selection or cell death occurs. Thus, the lifespan of double positive (CD4+CD8+; DP) thymocytes determines how many rounds of α chain rearrangement can be carried out and influences the likelihood of completing positive selection. The anti-apoptotic protein Bcl-xL is the ultimate effector regulating the survival of CD4+CD8+ thymocytes subject to the selection process, and the deletion of Bcl-xL leads to premature apoptosis of thymocytes prior to the completion of the developmental process. In addition to its critical function in the thymus, Bcl-xL also regulates the survival of peripheral T cells. Upon engagement with antigens, T cells are activated and differentiated into effectors. Activated T cells upregulate Bcl-xL to enhance their own survival. Bcl-xL-mediated survival is required for the generation of effectors that carry out the actual immune responses. In the absence of Bcl-xL, mature T cells undergo apoptosis prior to the completion of the differentiation process to become effector cells. Therefore, Bcl-xL ensures the survival of both developing and peripheral T cells, which is essential for a functional immune system. |
| format | Article |
| id | doaj-art-e69f4586893f4491bbca41065ba709fc |
| institution | Kabale University |
| issn | 1740-2522 1740-2530 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical and Developmental Immunology |
| spelling | doaj-art-e69f4586893f4491bbca41065ba709fc2025-02-03T05:48:14ZengWileyClinical and Developmental Immunology1740-25221740-25302012-01-01201210.1155/2012/632837632837Developing and Activated T Cell Survival Depends on Differential Signaling Pathways to Regulate Anti-Apoptotic Bcl-xLRuiqing Wang0Huimin Xie1Zhaofeng Huang2Weirong Shang3Zuoming Sun4Division of Immunology, Beckman Research Institute of the City of Hope, 1500 East Duarte Road, Duarte, CA 91010, USADepartment of Microbiology and Immunology, Medical School of the University of Illinois, Chicago, IL 60612, USAInstitute of Human Virology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, 510080, ChinaDepartment of Gynecology and Obstetrics, Emory University School of Medicine, 550 Peachtree Street, Suite 1800, Atlanta, GA 30308, USADivision of Immunology, Beckman Research Institute of the City of Hope, 1500 East Duarte Road, Duarte, CA 91010, USASurvival of T cells in both the central and peripheral immune system determines its ultimate function in the regulation of immune responses. In the thymus, developing T cells undergo positive and negative selection to generate a T cell repertoire that responds to foreign, but not self, antigens. During T cell development, the T cell receptor α chain is rearranged. However, the first round of rearrangement may fail, which triggers another round of α chain rearrangement until either successful positive selection or cell death occurs. Thus, the lifespan of double positive (CD4+CD8+; DP) thymocytes determines how many rounds of α chain rearrangement can be carried out and influences the likelihood of completing positive selection. The anti-apoptotic protein Bcl-xL is the ultimate effector regulating the survival of CD4+CD8+ thymocytes subject to the selection process, and the deletion of Bcl-xL leads to premature apoptosis of thymocytes prior to the completion of the developmental process. In addition to its critical function in the thymus, Bcl-xL also regulates the survival of peripheral T cells. Upon engagement with antigens, T cells are activated and differentiated into effectors. Activated T cells upregulate Bcl-xL to enhance their own survival. Bcl-xL-mediated survival is required for the generation of effectors that carry out the actual immune responses. In the absence of Bcl-xL, mature T cells undergo apoptosis prior to the completion of the differentiation process to become effector cells. Therefore, Bcl-xL ensures the survival of both developing and peripheral T cells, which is essential for a functional immune system.http://dx.doi.org/10.1155/2012/632837 |
| spellingShingle | Ruiqing Wang Huimin Xie Zhaofeng Huang Weirong Shang Zuoming Sun Developing and Activated T Cell Survival Depends on Differential Signaling Pathways to Regulate Anti-Apoptotic Bcl-xL Clinical and Developmental Immunology |
| title | Developing and Activated T Cell Survival Depends on Differential Signaling Pathways to Regulate Anti-Apoptotic Bcl-xL |
| title_full | Developing and Activated T Cell Survival Depends on Differential Signaling Pathways to Regulate Anti-Apoptotic Bcl-xL |
| title_fullStr | Developing and Activated T Cell Survival Depends on Differential Signaling Pathways to Regulate Anti-Apoptotic Bcl-xL |
| title_full_unstemmed | Developing and Activated T Cell Survival Depends on Differential Signaling Pathways to Regulate Anti-Apoptotic Bcl-xL |
| title_short | Developing and Activated T Cell Survival Depends on Differential Signaling Pathways to Regulate Anti-Apoptotic Bcl-xL |
| title_sort | developing and activated t cell survival depends on differential signaling pathways to regulate anti apoptotic bcl xl |
| url | http://dx.doi.org/10.1155/2012/632837 |
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