Development of V alpha 14(+) NK T cells in the early stages of embryogenesis

The majority of T lymphocytes start to develop at around day 15 of gestation (d15)-d17 in the thymus and comprise the peripheral repertoire characterized by the expression of polymorphic T-cell antigen receptors (TCRs). Contrary to these conventional T cells, a subset of T cells, called natural killer (NK) T cells (most of them expressing an invariant TCR encoded by the V alpha 14J alpha 281 gene with a 1-nt N-region), preferentially differentiates extrathymically and dominates the peripheral T-cell population at a high frequency (5% in splenic T cells and 40% in bone marrow T cells). sere, we investigated the development of NK T cells and found that the invariant V alpha 14(+) TCR transcripts and the circular DNA created by V alpha 14 and J alpha 281 gene rearrangements can be detected in the embryo body at d9.5 of gestation and in the yolk sac and the fetal liver at d11.5-d13.5 of gestation, but not in the thymus, whereas T cells with V alpha 1(+) TCR expression, a major population in the thymus, were not observed at these early stages of gestation, Fluorescence-activated cell sorter analysis also demonstrated that there exist CD3(+) alpha beta(+) T cells, almost all of which are V alpha 14/V beta 8(+) T cells, during early embryogenesis. To our knowledge, this demonstrates for the first time that a T lymphocyte subset develops in extrathymic tissues during the early stages of embryogenesis.