title: Developing and activated T cell survival depends on differential signaling pathways to regulate anti-apoptotic Bcl-x(L).
abstract: 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-x(L) is the ultimate effector regulating the survival of CD4(+)CD8(+) thymocytes subject to the selection process, and the deletion of Bcl-x(L) leads to premature apoptosis of thymocytes prior to the completion of the developmental process. In addition to its critical function in the thymus, Bcl-x(L) 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-x(L) to enhance their own survival. Bcl-x(L)-mediated survival is required for the generation of effectors that carry out the actual immune responses. In the absence of Bcl-x(L), mature T cells undergo apoptosis prior to the completion of the differentiation process to become effector cells. Therefore, Bcl-x(L) ensures the survival of both developing and peripheral T cells, which is essential for a functional immune system.
authors.affiliation: Division of Immunology, Beckman Research Institute of the City of Hope, 1500 East Duarte Road, Duarte, CA 91010, USA.
authors.forename: Ruiqing
authors.initials: R
authors.lastname: Wang
authors.forename: Huimin
authors.initials: H
authors.lastname: Xie
authors.forename: Zhaofeng
authors.initials: Z
authors.lastname: Huang
authors.forename: Weirong
authors.initials: W
authors.lastname: Shang
authors.forename: Zuoming
authors.initials: Z
authors.lastname: Sun
mesh_terms: D017209:Apoptosis / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology / Q000378:metabolism; D016827:CD8 Antigens / Q000276:immunology / Q000378:metabolism; D002470:Cell Survival / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D060168:Thymocytes / Q000276:immunology / Q000378:metabolism; D051020:bcl-X Protein / Q000276:immunology* / Q000378:metabolism
chemical_list: D015704:CD4 Antigens; D016827:CD8 Antigens; D051020:bcl-X Protein