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Prepublished online as a Blood First Edition Paper on September 5, 2002; DOI 10.1182/blood-2002-03-0744.
Submitted March 11, 2002
Accepted August 27, 2002
Involvement of p38 mitogen activated protein kinase in different stages of thymocyte development
Shu-Ching Hsu, Chia-Cheng Wu, Jiahuai Han, and Ming-Zong Lai*
Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan; Graduate Institute of Immunology, National Taiwan University, Taipei, Taiwan; Graduate Institute of Microbiology and Immunology, National Yang-Ming Univeristy, Taipei, Taiwan
Graduate Institute of Immunology, National Taiwan University, Taipei, Taiwan; Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan
Department of Immunology, Scripps Research Institute, La Jolla, CA, USA; Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan
* Corresponding author; email: mblai{at}ccvax.sinica.edu.tw.
Positive selection of thymocytes during T cell development is mediated by T cell receptor (TCR)-activated signals. For different mitogen activated protein kinases (MAPKs) activated by TCR complex, a selective involvement of extracellular signal-regulated kinase (ERK) but not p38 MAPK in positive selection has been suggested. Using transgenic mice with dominant negative mutant of both MAP kinase kinase 3 (MMK3) and MKK6, we obtained mice with different extents of inhibition on p38 MAPK activation. Partial inhibition of p38 MAPK impaired CD4-CD8- thymocyte development and T cell proliferation, but not positive selection. Interference of thymocyte positive selection was observed in mice with effective suppression of p38 MAPK. Our results suggest that, in addition to early thymocyte development, p38 is involved in positive selection.
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