Early T lineage progenitors (ETPs) in the thymus are thought to develop from common lymphoid progenitors (CLPs) in the bone marrow (BM). We compared thymic ETPs to BM CLPs in mice and found that they differed in several respects. Thymic ETPs were not interleukin 7 (IL-7)-responsive and generated B lineage progeny with delayed kinetics, whereas BM CLPs were IL-7-responsive and rapidly generated B cells. ETPs sustained production of T lineage progeny for longer periods of time than BM CLPs. Analysis of Ikaros-deficient mice that exhibit ongoing thymopoiesis without B lymphopoeisis revealed near-normal frequencies of thymic ETPs, yet undetectable numbers of BM CLPs. We conclude that ETPs can develop via a CLP-independent pathway.

• Novel coronavirus, SARS-CoV-2 is responsible for coronavirus disease 2019 (COVID-19). • SARS-CoV-2 has caused for human-tohuman transmission worldwide. • Non-pharmaceutical interventions (NPIs) can reduce the transmission of COVID-19. • COVID-19 is a crisis for massive health hazard, big humanitarian and development. • The use of research-based evidence, global response and solidarity may be helpful.

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Invariant NKT (iNKT) cells recognize glycolipid Ags, such as the marine sponge-derived glycosphingolipid ␣-galactosylceramide (␣GalCer) presented by the CD1d protein. In vivo activation of iNKT cells with ␣GalCer results in robust cytokine production, followed by the acquisition of an anergic phenotype. Here we have investigated mechanisms responsible for the establishment of ␣GalCer-induced iNKT cell anergy. We found that ␣GalCer-activated iNKT cells rapidly up-regulated expression of the inhibitory costimulatory receptor programmed death (PD)-1 at their cell surface, and this increased expression was retained for at least one month. Blockade of the interaction between PD-1 and its ligands, PD-L1 and PD-L2, at the time of ␣GalCer treatment prevented the induction iNKT cell anergy, but was unable to reverse established iNKT cell anergy. Consistently, injection of ␣GalCer into PD-1-deficient mice failed to induce iNKT cell anergy. However, blockade of the PD-1/PD-L pathway failed to prevent bacterial-or sulfatide-induced iNKT cell anergy, suggesting additional mechanisms of iNKT cell tolerance. Finally, we showed that blockade of PD-1/PD-L interactions enhanced the antimetastatic activities of ␣GalCer. Collectively, our findings reveal a critical role for the PD-1/PD-L costimulatory pathway in the ␣GalCer-mediated induction of iNKT cell anergy that can be targeted for the development of immunotherapies.