TY - JOUR
T1 - The c-kit+ maturation pathway in mouse thymic T cell development
T2 - Lineages and selection
AU - Akashi, Koichi
AU - Weissman, Irving L.
N1 - Funding Information:
We thank L. Jerabek for intrathymic injection and capable laboratory management, V. Braunstein for antibody preparation, and E. Lagasse, M. Amano, N. Watanabe, Y. Fukui, J. Domen, N. Uchida, A. Sen-Majumdar, and M. Lieberman for helpful discussion. Thanks to T. Knaak and J. Sun for their operation of the FACS machines used in these experiments, and to L. Hidalgo for animal care. K. A. is a research fellow in the Japanese Society for the Promotion of Science. This work was mainly supported by United States Public Health Service grant (CA-42551), and in part by a joint grant from Systemix and Sandoz, and a grant from the Ministry of Education, Science and Culture in Japan.
PY - 1996/8
Y1 - 1996/8
N2 - Positive selection of T cells begins with TCRαβ(lo) thymic progenitors. Here, we show that the most efficient TCR(lo) progenitors are c-kits with intermediate levels of CD4 and CD8 (DP(int). Positive selection of DP(int) TCR(lo) c-kit+ cells results in TCR(med) CD69+ c-kit+ transitional intermediates that show increased TCRVβ frequencies to selecting superantigen (SAg) that are committed to the CD4 or CD8 pathway. The cells on the c-kit+ maturation pathway maintain Bcl-2 expression. Most DP(int) c-kit+ progenitors fail positive selection, and become DP(hi) c-kit- cells that lose Bcl-2 expression. Some DP(hi) c-kit- blast cells can be salvaged to produce mature single-positive (SP) cells. DP(int) c-kit+ maturation to SP cells can occur in <12 hr in vitro on thymic stromal monolayers.
AB - Positive selection of T cells begins with TCRαβ(lo) thymic progenitors. Here, we show that the most efficient TCR(lo) progenitors are c-kits with intermediate levels of CD4 and CD8 (DP(int). Positive selection of DP(int) TCR(lo) c-kit+ cells results in TCR(med) CD69+ c-kit+ transitional intermediates that show increased TCRVβ frequencies to selecting superantigen (SAg) that are committed to the CD4 or CD8 pathway. The cells on the c-kit+ maturation pathway maintain Bcl-2 expression. Most DP(int) c-kit+ progenitors fail positive selection, and become DP(hi) c-kit- cells that lose Bcl-2 expression. Some DP(hi) c-kit- blast cells can be salvaged to produce mature single-positive (SP) cells. DP(int) c-kit+ maturation to SP cells can occur in <12 hr in vitro on thymic stromal monolayers.
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U2 - 10.1016/S1074-7613(00)80491-4
DO - 10.1016/S1074-7613(00)80491-4
M3 - Article
C2 - 8769478
AN - SCOPUS:0030218969
SN - 1074-7613
VL - 5
SP - 147
EP - 161
JO - Immunity
JF - Immunity
IS - 2
ER -
