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Science 307 (5711): 925-928

Copyright © 2005 by the American Association for the Advancement of Science

Lymphotoxin-Mediated Regulation of {gamma}{delta} Cell Differentiation by {alpha}ß T Cell Progenitors

Bruno Silva-Santos,* Daniel J. Pennington,*{dagger} Adrian C. Hayday{dagger}

Abstract: The thymus gives rise to two T cell lineages, {alpha}ß and {gamma}{delta}, that are thought to develop independently of one another. Hence, double positive (DP) thymocytes expressing CD4 and CD8 coreceptors are usually viewed simply as progenitors of CD4+ and CD8+ {alpha}ß T cells. Instead we report that DP cells regulate the differentiation of early thymocyte progenitors and {gamma}{delta} cells, by a mechanism dependent on the transcription factor RORgt, and the lymphotoxin (LT) ß receptor (LTßR). This finding provokes a revised view of the thymus, in which lymphoid tissue induction-type processes coordinate the developmental and functional integration of the two T cell lineages.

Peter Gorer Department of Immunobiology, Guy's King's St. Thomas' Medical School, King's College, Guy's Hospital, London SE1 9RT, UK.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: daniel.pennington{at}kcl.ac.uk (D.J.P.), adrian.hayday{at}kcl.ac.uk (A.C.H.)

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