Evidence That {gamma}{delta} versus {alpha}{beta} T Cell Fate Determination Is Initiated Independently of T Cell Receptor Signaling

doi:10.1084/jem.193.6.689

Published online 19 March 2001.

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© The Rockefeller University Press, 0022-1007/2001/3/689/ $5.00
The Journal of Experimental Medicine, Volume 193, Number 6, March 19, 2001 689-698

Original Article

Evidence That ${gamma}$ ${delta}$ versus ${alpha}$ β T Cell Fate Determination Is Initiated Independently of T Cell Receptor Signaling

Joonsoo Kang^b, Ariane Volkmann^a, and David H. Raulet^a

^a Department of Molecular and Cellular Biology, Cancer Research Laboratory, Division of Immunology, University of California at Berkeley, Berkeley, California 94720
^b University of Massachusetts Medical School, Department of Pathology, Worcester, Massachusetts 01655
Department of Molecular and Cellular Biology, and Cancer Research Laboratory, Division of Immunology, 489 Life Sciences Addition, University of California at Berkeley, Berkeley, CA 94720.510-642-1443510-642-9522

raulet{at}uclink4.berkeley.edu

Two types of T cells, ${alpha}$ β and ${gamma}$ ${delta}$ , develop in vertebrates. Howthese two T cell lineages arise from a common thymic T progenitoris poorly understood. Differentiation of ${alpha}$ β lineage T cellsrequires the surrogate ${alpha}$ chain (pT ${alpha}$ ), which associates with theT cell receptor (TCR) β chain to form the pre-TCR. ${gamma}$ ${delta}$ lineagedevelopment does not appear to involve an obligatory surrogatechain, but instead requires productive rearrangement and expressionof both TCR ${gamma}$ and ${delta}$ genes. It has been proposed that the qualityof signals transmitted by the pre-TCR and ${gamma}$ ${delta}$ TCR are distinctand that these "instructive" signals determine the lineage fateof an uncommitted progenitor cell. Here we show that the thymicT progenitor cells (CD25⁺CD44⁺c-kit⁺CD3^–CD4^–CD8^–thymocytes, termed pro-T cells) from young adult mice that haveyet to express TCRs can be subdivided based on interleukin 7receptor (IL-7R) expression. These subsets exhibit differentialpotential to develop into ${gamma}$ ${delta}$ versus ${alpha}$ β lineage (CD4⁺CD8⁺ cells)in the thymus. Upon intrathymic injection, IL-7R^neg-lo pro-Tcells generated a 13-fold higher ratio of ${alpha}$ β lineage to ${gamma}$ ${delta}$ lineage cells than did IL-7R⁺ pro-T cells. Much of this differencewas due to a fivefold greater potential of IL-7R⁺ pro-T cellsto develop into TCR- ${gamma}$ ${delta}$ T cells. Evidence indicates that this biaseddevelopmental potential is not a result of enhanced TCR- ${gamma}$ generearrangement/expression in IL-7R⁺ pro-T cells. These resultsindicate that the pro-T cells are heterogeneous in developmentalpotential before TCR gene rearrangement and suggest that insome precursor cells the initial lineage commitment is independentof TCR-mediated signals.

Key Words: T cell development • IL-7 • T precursor cells • lineage commitment • T cell receptor gene rearrangement

Abbreviations used in this paper: APC, allophycocyanin; BrdU,bromodeoxyuridine; B6, C57BL/6; DC, dendritic cell; DN, doublenegative; FTOC, fetal thymic organ culture; RT, reverse transcription;SCF, stem cell factor; TN, triple negative.

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