T cells are derived from progenitor thymocytes, of which only a minority receive the appropriate TCR signal, undergo positive selection and mature. Owing to the very short lifespan of thymocytes, the prerequisite for ...T cells are derived from progenitor thymocytes, of which only a minority receive the appropriate TCR signal, undergo positive selection and mature. Owing to the very short lifespan of thymocytes, the prerequisite for posi- tive selection is survival. TCR signal-induced Bcl-2 expression is believed to play a dominant role in the survival of positively selecting thymocytes, but how Bcl-2 is directly regulated is unknown. Here we report that the immediate early gene （IEG） c-Fos can stimulate the expression of Bcl-2, depending on a specific AP-l-binding site in the Bcl-2 promoter. In c-Fos transgenic （Fos-Tg） mice, c-Fos binds to this site and promotes the expression of Bcl-2. As a result, Fos-Tg thymocytes exhibited enhanced survival, and more mature single-positive （SP） thymocytes were generated, even on a unique TCR background. The TCR repertoire remained normal in Fos-Tg mice. Our results identified c-Fos as the mediator of the stimulatory effect of TCR signaling on Bcl-2 expression. Therefore, c-Fos, as an IEG, because of its early response ability, can quickly rescue the survival of short-lived thymocytes during positive selection. Our results provide novel insight into the mechanism regulating the survival of positively selecting thymocytes.展开更多
After positive selection and lineage commitment,the TCRαβ^+CD4/CD8 SP medullary thymocytes migrate into and reside in thymic medulla,where they undergo an ordered program of late stage of T cell functional maturatio...After positive selection and lineage commitment,the TCRαβ^+CD4/CD8 SP medullary thymocytes migrate into and reside in thymic medulla,where they undergo an ordered program of late stage of T cell functional maturation and negative selection to delete self-reactive clones by apoptosis.Accomplishment of this final differentiation pathway,a physiological T cell repertoire is formed:T cells acquire immunocompetence to respond to foreign antigens and tolerance to self-antigens,ready for the emigration to homing to the T cell regions of peripheral lymphoid organs and tissues.In this review,emphases are put on introducing the approaches applied in this area and our own observations.Basically,we have analyzed the late stage of medullary thymocyte phenotypic differentiation pathways of both CD4 SP and CD8 SP medullary thymocytes and the concomitant functional maturation pathway,in particular,of CD4 SP thymocytes.It is to provide a standard to compare the functional capacity of the cells at the developmental stages induced by different conditions.The cellular and molecular basis of this differentiation process has been partially described.Cellular & Molecular Immunology.2004;1(1):3-11.展开更多
文摘T cells are derived from progenitor thymocytes, of which only a minority receive the appropriate TCR signal, undergo positive selection and mature. Owing to the very short lifespan of thymocytes, the prerequisite for posi- tive selection is survival. TCR signal-induced Bcl-2 expression is believed to play a dominant role in the survival of positively selecting thymocytes, but how Bcl-2 is directly regulated is unknown. Here we report that the immediate early gene （IEG） c-Fos can stimulate the expression of Bcl-2, depending on a specific AP-l-binding site in the Bcl-2 promoter. In c-Fos transgenic （Fos-Tg） mice, c-Fos binds to this site and promotes the expression of Bcl-2. As a result, Fos-Tg thymocytes exhibited enhanced survival, and more mature single-positive （SP） thymocytes were generated, even on a unique TCR background. The TCR repertoire remained normal in Fos-Tg mice. Our results identified c-Fos as the mediator of the stimulatory effect of TCR signaling on Bcl-2 expression. Therefore, c-Fos, as an IEG, because of its early response ability, can quickly rescue the survival of short-lived thymocytes during positive selection. Our results provide novel insight into the mechanism regulating the survival of positively selecting thymocytes.
文摘After positive selection and lineage commitment,the TCRαβ^+CD4/CD8 SP medullary thymocytes migrate into and reside in thymic medulla,where they undergo an ordered program of late stage of T cell functional maturation and negative selection to delete self-reactive clones by apoptosis.Accomplishment of this final differentiation pathway,a physiological T cell repertoire is formed:T cells acquire immunocompetence to respond to foreign antigens and tolerance to self-antigens,ready for the emigration to homing to the T cell regions of peripheral lymphoid organs and tissues.In this review,emphases are put on introducing the approaches applied in this area and our own observations.Basically,we have analyzed the late stage of medullary thymocyte phenotypic differentiation pathways of both CD4 SP and CD8 SP medullary thymocytes and the concomitant functional maturation pathway,in particular,of CD4 SP thymocytes.It is to provide a standard to compare the functional capacity of the cells at the developmental stages induced by different conditions.The cellular and molecular basis of this differentiation process has been partially described.Cellular & Molecular Immunology.2004;1(1):3-11.
