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ß and 
Thymocyte Development1
*
Section of Immunobiology and
Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520
Janus kinase 3 (Jak3) plays a central role in the transduction of
signals mediated by the IL-2 family of cytokine receptors. Targeted
deletion of the murine Jak3 gene results in severe reduction of 
ß
and complete elimination of 
lineage thymocytes and NK cells. The
developmental blockade appears to be imposed on early thymocyte
differentiation and/or expansion. In this study, we show that
bcl-2 expression and in vivo survival of immature
thymocytes are greatly compromised in Jak3-/- mice. There
is no gross deficiency in rearrangements of the TCR and
certain loci in pre-T cells, and a functional TCR transgene
cannot rescue lineage differentiation in Jak3-/-
mice. In contrast, a TCRß transgene is partially able to restore
ß thymocyte development. These data suggest that the signals
mediated by Jak3 are critical for survival of all thymocyte precursors
particularly during TCRß-chain gene rearrangement, and are
continuously required in the lineage. The results also emphasize
the fundamentally different requirements for differentiation of the
ß and T cell lineages.
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