Abstract
Long-term impairment in T cell–mediated adaptive immunity is a major clinical obstacle following treatment of blood disorders with hematopoietic stem cell transplantation. Although T cell development in the thymus has been extensively characterized, there are significant gaps in our understanding of prethymic processes that influence early T cell potential. We have uncovered a Notch/IL-21 signaling axis in bone marrow common lymphoid progenitor (CLP) cells. IL-21 receptor expression was driven by Notch activation in CLPs, and in vivo treatment with IL-21 induced Notch-dependent CLP proliferation. Taking advantage of this potentially novel signaling axis, we generated T cell progenitors ex vivo, which improved repopulation of the thymus and peripheral lymphoid organs of mice in an allogeneic transplant model. Importantly, Notch and IL-21 activation were equally effective in the priming and expansion of human cord blood cells toward the T cell fate, confirming the translational potential of the combined treatment.
Authors
Kilian Sottoriva, Na Yoon Paik, Zachary White, Thilinie Bandara, Lijian Shao, Teruyuki Sano, Kostandin V. Pajcini
This file is in Adobe Acrobat (PDF) format. If you have not installed and configured the Adobe Acrobat Reader on your system.
Having trouble reading a PDF?
PDFs are designed to be printed out and read, but if you prefer to read them online, you may find it easier if you increase the view size to 125%.
Having trouble saving a PDF?
Many versions of the free Acrobat Reader do not allow Save. You must instead save the PDF from the JCI Online page you downloaded it from. PC users: Right-click on the Download link and choose the option that says something like "Save Link As...". Mac users should hold the mouse button down on the link to get these same options.
Having trouble printing a PDF?
- Try printing one page at a time or to a newer printer.
- Try saving the file to disk before printing rather than opening it "on the fly." This requires that you configure your browser to "Save" rather than "Launch Application" for the file type "application/pdf", and can usually be done in the "Helper Applications" options.
- Make sure you are using the latest version of Adobe's Acrobat Reader.
