TY - JOUR
T1 - Two distinct pathways of positive selection for thymocytes
AU - Akashi, Koichi
AU - Kondo, Motonari
AU - Weissman, Irving L.
PY - 1998/3/3
Y1 - 1998/3/3
N2 - Most mouse thymocytes undergoing positive selection are found on one of two pathways; the c-Kit+ and the c-Kit- pathways. Here, we show that c-Kit and interleukin-7 receptor (IL-7R)-mediated signals support positive selection during the transition from the subpopulation that first expresses cell surface T cell receptor (TCR)- the TCRα/β1(o)CD4(int)/CD8(int) (DP (int)) c-Kit+ cells to TCRα/β(med) c-Kit+ transitional intermediate cells (the c-Kit+ pathway). Cells that fail positive selection on the c-Kit+ pathway become TCRα/β1(o)c-Kit- (DP(hi)) blasts that appear to undergo alternative TCRα rearrangements. The rare DP(hi)c-Kit- blast cells that thus are salvaged for positive selection by expressing a self-major histocompatibility complex selectable TCRα/β up-regulate IL-7R, but not c- Kit, and are the principal progenitors on the c-Kit- pathway; this c-Kit- IL-7R+ pathway is TCR1(o-med) c-Kit+ transition, but is not essential for CD4 lineage maturation from DP(hi) c-Kit- blasts. In this view, positive selection on the c-Kit- path results from a salvage of cells that failed positive selection on the c-Kit+ path.
AB - Most mouse thymocytes undergoing positive selection are found on one of two pathways; the c-Kit+ and the c-Kit- pathways. Here, we show that c-Kit and interleukin-7 receptor (IL-7R)-mediated signals support positive selection during the transition from the subpopulation that first expresses cell surface T cell receptor (TCR)- the TCRα/β1(o)CD4(int)/CD8(int) (DP (int)) c-Kit+ cells to TCRα/β(med) c-Kit+ transitional intermediate cells (the c-Kit+ pathway). Cells that fail positive selection on the c-Kit+ pathway become TCRα/β1(o)c-Kit- (DP(hi)) blasts that appear to undergo alternative TCRα rearrangements. The rare DP(hi)c-Kit- blast cells that thus are salvaged for positive selection by expressing a self-major histocompatibility complex selectable TCRα/β up-regulate IL-7R, but not c- Kit, and are the principal progenitors on the c-Kit- pathway; this c-Kit- IL-7R+ pathway is TCR1(o-med) c-Kit+ transition, but is not essential for CD4 lineage maturation from DP(hi) c-Kit- blasts. In this view, positive selection on the c-Kit- path results from a salvage of cells that failed positive selection on the c-Kit+ path.
UR - http://www.scopus.com/inward/record.url?scp=0032478068&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032478068&partnerID=8YFLogxK
U2 - 10.1073/pnas.95.5.2486
DO - 10.1073/pnas.95.5.2486
M3 - Article
C2 - 9482912
AN - SCOPUS:0032478068
VL - 95
SP - 2486
EP - 2491
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 5
ER -