Two distinct pathways of positive selection for thymocytes

Koichi Akashi, Motonari Kondo, Irving L. Weissman

Research output: Contribution to journalArticle

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

Fingerprint

Thymocytes
T-Cell Antigen Receptor
Interleukin-7 Receptors
Major Histocompatibility Complex
Up-Regulation

All Science Journal Classification (ASJC) codes

  • General

Cite this

Two distinct pathways of positive selection for thymocytes. / Akashi, Koichi; Kondo, Motonari; Weissman, Irving L.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 95, No. 5, 03.03.1998, p. 2486-2491.

Research output: Contribution to journalArticle

@article{eb0e78e481194cbd90da189c796f3106,
title = "Two distinct pathways of positive selection for thymocytes",
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.",
author = "Koichi Akashi and Motonari Kondo and Weissman, {Irving L.}",
year = "1998",
month = "3",
day = "3",
doi = "10.1073/pnas.95.5.2486",
language = "English",
volume = "95",
pages = "2486--2491",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "5",

}

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 -