PMID- 9482912
OWN - NLM
STAT- MEDLINE
DCOM- 19980409
LR  - 20190501
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 95
IP  - 5
DP  - 1998 Mar 3
TI  - Two distinct pathways of positive selection for thymocytes.
PG  - 2486-91
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 TCRalpha/betaloCD4(int)/CD8(int) (DPint) c-Kit+ cells to 
      TCRalpha/betamedc-Kit+ transitional intermediate cells (the c-Kit+ pathway). 
      Cells that fail positive selection on the c-Kit+ pathway become 
      TCRalpha/betaloc-Kit- (DPhi) blasts that appear to undergo alternative TCRalpha 
      rearrangements. The rare DPhic-Kit- blast cells that thus are salvaged for 
      positive selection by expressing a self-major histocompatibility complex 
      selectable TCRalpha/beta 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 mainly CD4 
      lineage committed. Cell division is a feature of the TCRlo-medc-Kit+ transition, 
      but is not essential for CD4 lineage maturation from DPhic-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.
FAU - Akashi, K
AU  - Akashi K
AD  - Departments of Pathology and Developmental Biology, Stanford University School of 
      Medicine, Stanford, CA 94305, USA. Akashi@Darwin.Stanford.edu
FAU - Kondo, M
AU  - Kondo M
FAU - Weissman, I L
AU  - Weissman IL
LA  - eng
GR  - CA-42551/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Antigens, CD)
RN  - 0 (Receptors, Antigen, T-Cell, alpha-beta)
RN  - 0 (Receptors, Interleukin)
RN  - 0 (Receptors, Interleukin-7)
RN  - 0 (beta 2-Microglobulin)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-kit)
SB  - IM
MH  - Animals
MH  - Antigens, CD/biosynthesis
MH  - CD4-Positive T-Lymphocytes/immunology
MH  - CD8-Positive T-Lymphocytes/immunology
MH  - Cell Division
MH  - Flow Cytometry
MH  - Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor
MH  - *Genes, MHC Class I
MH  - *Genes, MHC Class II
MH  - Haplotypes
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Proto-Oncogene Proteins c-kit/biosynthesis/genetics
MH  - Receptors, Antigen, T-Cell, alpha-beta/biosynthesis/*genetics/physiology
MH  - Receptors, Interleukin/biosynthesis
MH  - Receptors, Interleukin-7
MH  - Signal Transduction
MH  - T-Lymphocytes/*immunology
MH  - Thymus Gland/immunology
MH  - Up-Regulation/immunology
MH  - beta 2-Microglobulin/genetics
PMC - PMC19384
EDAT- 1998/04/16 00:00
MHDA- 1998/04/16 00:01
PMCR- 1998/09/03
CRDT- 1998/04/16 00:00
PHST- 1998/04/16 00:00 [pubmed]
PHST- 1998/04/16 00:01 [medline]
PHST- 1998/04/16 00:00 [entrez]
PHST- 1998/09/03 00:00 [pmc-release]
AID - 4172 [pii]
AID - 10.1073/pnas.95.5.2486 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1998 Mar 3;95(5):2486-91. doi: 10.1073/pnas.95.5.2486.