Two distinct pathways of positive selection for thymocytes

Koichi Akashi, Motonari Kondo, Irving L. Weissman

Research output: Contribution to journalArticlepeer-review

36 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2486-2491
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume95
Issue number5
DOIs
Publication statusPublished - Mar 3 1998
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General

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