Two distinct pathways of positive selection for thymocytes.

Important note: Information in this article was accurate in 1998. The state of the art may have changed since the publication date.

Two distinct pathways of positive selection for thymocytes.

Proc Natl Acad Sci U S A. 1998 Mar 3;95(5):2486-91. Unique Identifier : AIDSLINE MED/98151539
Akashi K; Kondo M; Weissman IL; Departments of Pathology and Developmental Biology, Stanford; University School of Medicine, Stanford, CA 94305, USA.; Akashi@Darwin.Stanford.edu

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 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.

Keywords: *Genes, MHC Class I *Genes, MHC Class II *Receptors, Antigen, T-Cell, alpha-beta/GENETICS *T-Lymphocytes/IMMUNOLOGY
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