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Thymocyte expansion and maturation: crosstalk of CD44v6 on thymocytes and panCD44 on stroma cells
Author(s) -
Rajasagi Mohini,
Marhaba Rachid,
Vitacolonna Mario,
Zöller Margot
Publication year - 2010
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1038/icb.2009.70
Subject(s) - thymocyte , biology , stroma , cd44 , progenitor cell , double negative , t cell , homing (biology) , progenitor , microbiology and biotechnology , immunology , haematopoiesis , cancer research , stem cell , cell , immune system , immunohistochemistry , ecology , genetics
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.