de La Coste Alix, Six Emmanuelle, Fazilleau Nicolas, Mascarell Laurent, Legrand Nicolas, Mailhé Marie-Pierre, Cumano Ana, Laâbi Yacine, Freitas Antonio A
Unité de Biologie des Populations Lymphocytaires, Centre National de la Recherche Scientifique, Unité de Recherche Associée 2582, Paris, France.
J Immunol. 2005 Mar 1;174(5):2730-7. doi: 10.4049/jimmunol.174.5.2730.
The role of Notch signaling in T cell commitment during lymphoid development is well established. However, the identity of the ligand that triggers this critical signal in vivo is still unclear. By overexpressing Delta-1 and Delta-4 ligands in the hemopoietic cells of athymic nu/nu host mice, we demonstrate that, in vivo and in the absence of a thymus, Delta-1 or Delta-4 expression is sufficient to promote T cell development from the most immature progenitor stages to complete maturation of both CD8(+) and CD4(+) alphabeta T cells. The mature T cells developing in a Delta-1- or Delta-4-enriched environment express a diverse TCR repertoire, are able to proliferate upon in vitro TCR stimulation, but show different profiles of cytokine production after in vitro anti-CD3 stimulation.
Notch信号在淋巴细胞发育过程中对T细胞定向分化的作用已得到充分证实。然而，在体内触发这一关键信号的配体身份仍不明确。通过在无胸腺nu/nu宿主小鼠的造血细胞中过表达Delta-1和Delta-4配体，我们证明，在体内且无胸腺的情况下，Delta-1或Delta-4的表达足以促进从最不成熟的祖细胞阶段到CD8(+)和CD4(+)αβ T细胞完全成熟的T细胞发育。在富含Delta-1或Delta-4的环境中发育的成熟T细胞表达多样化的TCR库，能够在体外TCR刺激下增殖，但在体外抗CD3刺激后显示出不同的细胞因子产生谱。
