Abstract:
:Alpha4-mediated signaling is involved in a variety of functions in mammalian cells. To determine whether this is true for immunocompetent cells, we generated mutant (Lck-alpha4-) mice in which the alpha4 gene was deleted in a T cell-specific manner using the Cre/loxP system. These mice showed impaired early T cell development. Thymi at most ages were small and their architecture was disorganized. This defect was not due to increased thymocyte apoptosis but to decreased cell proliferation. T cell development was found to be severely arrested at the CD4/CD8 double-negative 3 stage and the thymus contained very few double-positive or single-positive (SP) mature thymocytes. The mutant thymocytes showed impaired proliferative responses to anti-CD3 monoclonal antibody (mAb) stimulation or to the cytokines IL-2, IL-1 or TNF. In the spleen, the numbers of mature SP T cells were decreased and their proliferative responses to anti-CD3 plus IL-2 or to anti-CD28 mAb were impaired. A severe impairment of CD3-induced expression of CD25 was also observed. These data suggest that alpha4 plays a critical role in the proliferation of thymocytes, which is necessary for early T cell development.
journal_name
Eur J Immunoljournal_title
European journal of immunologyauthors
Hua DR,Inui S,Yamashita T,Maeda K,Takagi K,Takeda J,Sakaguchi Ndoi
10.1002/eji.200323720keywords:
subject
Has Abstractpub_date
2003-07-01 00:00:00pages
1899-906issue
7eissn
0014-2980issn
1521-4141journal_volume
33pub_type
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