Original Article

Evidence That versus ß T Cell Fate Determination Is Initiated Independently of T Cell Receptor Signaling

Correspondence to: David H. Raulet, 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. Tel:510-642-9522 Fax:510-642-1443 E-mail:raulet{at}uclink4.berkeley.edu.

Two types of T cells, ß and , develop in vertebrates. How these two T cell lineages arise from a common thymic T progenitor is poorly understood. Differentiation of ß lineage T cells requires the surrogate chain (pT), which associates with the T cell receptor (TCR) ß chain to form the pre-TCR. lineage development does not appear to involve an obligatory surrogate chain, but instead requires productive rearrangement and expression of both TCR and genes. It has been proposed that the quality of signals transmitted by the pre-TCR and TCR are distinct and that these "instructive" signals determine the lineage fate of an uncommitted progenitor cell. Here we show that the thymic T progenitor cells (CD25⁺CD44⁺c-kit⁺CD3^-CD4^-CD8^- thymocytes, termed pro-T cells) from young adult mice that have yet to express TCRs can be subdivided based on interleukin 7 receptor (IL-7R) expression. These subsets exhibit differential potential to develop into versus ß lineage (CD4⁺CD8⁺ cells) in the thymus. Upon intrathymic injection, IL-7R^neg-lo pro-T cells generated a 13-fold higher ratio of ß lineage to lineage cells than did IL-7R⁺ pro-T cells. Much of this difference was due to a fivefold greater potential of IL-7R⁺ pro-T cells to develop into TCR- T cells. Evidence indicates that this biased developmental potential is not a result of enhanced TCR- gene rearrangement/expression in IL-7R⁺ pro-T cells. These results indicate that the pro-T cells are heterogeneous in developmental potential before TCR gene rearrangement and suggest that in some precursor cells the initial lineage commitment is independent of TCR-mediated signals.

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

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