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Published Online December 9, 2004
Science DOI: 10.1126/science.1103978

Reports

Submitted on August 12, 2004
Accepted on November 24, 2004

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

Bruno Silva-Santos 1, Daniel J. Pennington 1*, Adrian C. Hayday 1*

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

* To whom correspondence should be addressed.
Daniel J. Pennington , E-mail: daniel.pennington{at}kcl.ac.uk
Adrian C. Hayday , E-mail: adrian.hayday{at}kcl.ac.uk

The thymus gives rise to two T cell lineages, {alpha}{beta} and {gamma}{delta}, thought to develop independently of one another. Hence double positive (DP) thymocytes expressing CD4 and CD8 co-receptors are usually viewed simply as progenitors of CD4+ and CD8+ {alpha}{beta} 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 ROR{gamma}t, and the lymphotoxin (LT) {beta} receptor (LT{beta}R). This 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.


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