Developmental hematopoiesis: innate programming of αβ T cells

During the development of the immune system, there is a progressive shift from fast-acting innate-like lymphocytes to slower-acting adaptive lymphocytes. This developmental shift is evident in B cells, γδ T cells, and αβ T cells, with the more innate-like lineages (B1a, B1b, Vδ1, virtual memory CD8+, iNKT, and CD8αα) being produced before the more adaptive lineages (B2, Vγ9Vδ2, and conventional CD8+ and CD4+ αβ T cells). However, immunologists have historically viewed the development of B and γδ T cells differently than αβ T cells. Whereas it is well accepted that the functions of B and γδ T cells are linked to their derivation from distinct hematopoietic progenitors that arise throughout ontogeny, the same phenomenon has largely been ignored for αβ T cells. Instead, the prevailing view is that all αβ T cells are made from the same hematopoietic stem cells (HSCs), and any diversity in the αβ T-cell compartment comes from stochastic expression of different TCRs and random environmental cues encountered in the thymus. In this review, we discussed the evidence that αβ T-cell lineage decisions are not solely determined by thymic selection and that hematopoietic origin also intrinsically biases development toward innate-like T cells in early life.