Thymocyte expansion and maturation

• Verfasst von: Rajasagi, Mohini [VerfasserIn]
• Verfasst von: Marhaba, Rachid [VerfasserIn]
• Verfasst von: Vitacolonna, Mario [VerfasserIn]
• Verfasst von: Zöller, Margot [VerfasserIn]
• Titel: Thymocyte expansion and maturation
• Titelzusatz: crosstalk of CD44v6 on thymocytes and panCD44 on stroma cells
• Verf.angabe: Mohini Rajasagi, Rachid Marhaba, Mario Vitacolonna and Margot Zöller
• E-Jahr: 2010
• Jahr: February 2010
• Umfang: 12 S.
• Fussnoten: Online veröffentlicht 29. September 200 ; Gesehen am 10.05.2023
• Titel Quelle: Enthalten in: Immunology & cell biology
• Ort Quelle: Hoboken, NJ : Wiley, 1987
• Jahr Quelle: 2010
• Band/Heft Quelle: 88(2010), 2 vom: Feb., Seite 136-147
• ISSN Quelle: 1440-1711
• DOI: doi:10.1038/icb.2009.70
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: adhesion molecules
• Sach-SW: rodent
• Sach-SW: signal transduction
• Sach-SW: thymocyte maturation
• K10plus-PPN: 1844963276

Abstract

Re-acquisition of immunocompetence after allogeneic bone marrow cell (BMC) transplantation depends on intrathymic maturation of the allogeneic T progenitor cells. We recently reported that CD44 promotes progenitor homing into the thymus and T-cell maturation and now elucidate the molecular mechanisms of CD44-supported thymocyte maturation. Lethally irradiated, tumor-bearing mice, allogeneically reconstituted with T-cell-depleted BMC and a small number of common lymphoid progenitor 2 cells (CLP2) from transgenic (TG) mice, that express ratCD44v4-v7 under the Thy1 promoter, showed accelerated immunocompetent T-cell recovery compared with mice reconstituted with non-transgenic (NTG) CLP2. In addition, graft-versus-host disease was strongly reduced after tumor vaccination. TG, but not NTG double-negative (DN) thymocytes showed high proliferative potential, accompanied by constitutive association of lck with CD44. Importantly, when thymocyte adhesion was strengthened by anti-CD44, co-cultures of DN thymocytes with thymic stroma supported DN thymocyte maturation. The close contact between DN thymocytes and thymic stroma promoted persisting activation of lck and ERK1/2, particularly in CD44v6+ DN thymocytes. Thus, intrathymic T-cell maturation in allogeneically reconstituted, leukemia-bearing hosts can be considerably accelerated by high CD44v6 expression in early thymocytes, in which proliferation-supporting signals are initiated by a crosstalk between CD44v6 on thymocytes and panCD44 on the thymic stroma.