Document Detail


Thymocyte expansion and maturation: crosstalk of CD44v6 on thymocytes and panCD44 on stroma cells.
MedLine Citation:
PMID:  19786978     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Mohini Rajasagi; Rachid Marhaba; Mario Vitacolonna; Margot Z?ller
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-09-29
Journal Detail:
Title:  Immunology and cell biology     Volume:  88     ISSN:  1440-1711     ISO Abbreviation:  Immunol. Cell Biol.     Publication Date:  2010 Feb 
Date Detail:
Created Date:  2010-02-18     Completed Date:  2010-05-18     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8706300     Medline TA:  Immunol Cell Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  136-47     Citation Subset:  IM    
Affiliation:
Department of Tumor Cell Biology, University Hospital of Surgery and German Cancer Research Center, Heidelberg, Germany.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigens, CD44 / metabolism*
Cell Adhesion
Cell Differentiation*
Cell Proliferation
Cells, Cultured
Coculture Techniques
Graft vs Host Disease / immunology
Immune Tolerance / immunology
Immunocompetence / immunology
Mice
Neoplasms / immunology,  pathology
Rats
Signal Transduction
Spleen / cytology,  immunology
Stromal Cells / cytology,  immunology*
T-Lymphocytes / cytology*,  immunology*
Thymus Gland / cytology,  immunology
Time Factors
Chemical
Reg. No./Substance:
0/Antigens, CD44; 0/CD44v6 antigen

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