NKT cells derive from double-positive thymocytes that are positively selected by CDId

CDId-reactive NKT cells are a separate T cell sublineage. Instructive model s propose that NKT cells branch off the mainstream developmental pathway be cause of their T cell antigen receptor specificity, whereas stochastic mode ls would propose that they develop from precursor cells committed to this s ublineage before variable-gene rearrangement. We show here that immature do uble-positive (DP) thymocytes form the canonical rearranged V-alpha gene of NKT cells at nearly equivalent frequencies in the presence or absence of C DId expression. After interacting with CDId in the thymus, these cells give rise to expanded populations of NKT cells - including both CD4(+) and doub le-negative lymphocytes in the thymus and periphery - that express this alp ha chain. These results confirm the existence of a DP intermediate for CDId -reactive NKT cells. They also show that the early developmental stages of these T cells are not governed by a distinct mechanism, which is consistent with the TCR-instructive model of differentiation.