Prigione Ignazia, Benvenuto Federica, Bocca Paola, Battistini Luca, Uccelli Antonio, Pistoia Vito
Istituto di Ricovero e Cura a Carattere Scientifico G. Gaslini, Genoa, Italy.
Stem Cells. 2009 Mar;27(3):693-702. doi: 10.1634/stemcells.2008-0687.
The immunomodulatory activities of human mesenchymal stem cells (MSCs) provide a rational basis for their application in the treatment of immune-mediated diseases, such as graft versus host disease and multiple sclerosis. The effects of MSCs on invariant natural killer T (iNKT) and gammadelta T cells, both involved in the pathogenesis of autoimmune diseases, are unknown. Here, we investigated the effects of MSCs on in vitro expansion of these unconventional T-cell populations. MSCs inhibited iNKT (Valpha24(+)Vbeta11(+)) and gammadelta T (Vdelta2(+)) cell expansion from peripheral blood mononuclear cells in both cell-to-cell contact and transwell systems. Such inhibition was partially counteracted by indomethacin, a prostaglandin E(2) inhibitor. Block of indoleamine 2,3-deoxygenase and transforming growth factor beta1 did not affect Valpha24(+)Vbeta11(+) and Vdelta2(+) cell expansion. MSCs inhibited interferon-gamma production by activated Valpha24(+)Vbeta11(+) and impaired CD3-mediated proliferation of activated Valpha24(+)Vbeta11(+) and Vdelta2(+) T cells, without affecting their cytotoxic potential. MSCs did not inhibit antigen processing/presentation by activated Vdelta2(+) T cells to CD4(+) T cells. In contrast, MSCs were lysed by activated Vdelta2(+) T cells through a T-cell receptor-dependent mechanism. These results are translationally relevant in view of the increasing interest in MSC-based therapy of autoimmune diseases.
人间充质干细胞（MSCs）的免疫调节活性为其在治疗免疫介导疾病（如移植物抗宿主病和多发性硬化症）中的应用提供了合理依据。MSCs对均参与自身免疫性疾病发病机制的不变自然杀伤T细胞（iNKT）和γδT细胞的影响尚不清楚。在此，我们研究了MSCs对这些非常规T细胞群体体外扩增的影响。在细胞间接触和transwell系统中，MSCs均抑制外周血单个核细胞中iNKT（Valpha24(+)Vbeta11(+)）和γδT（Vdelta2(+)）细胞的扩增。吲哚美辛（一种前列腺素E2抑制剂）可部分抵消这种抑制作用。吲哚胺2,3-双加氧酶和转化生长因子β1的阻断并不影响Valpha24(+)Vbeta11(+)和Vdelta2(+)细胞的扩增。MSCs抑制活化的Valpha24(+)Vbeta11(+)产生干扰素-γ，并损害活化的Valpha24(+)Vbeta11(+)和Vdelta2(+)T细胞的CD3介导的增殖，而不影响它们的细胞毒性潜力。MSCs不抑制活化的Vdelta2(+)T细胞向CD4(+)T细胞的抗原加工/呈递。相反，活化的Vdelta2(+)T细胞通过T细胞受体依赖性机制裂解MSCs。鉴于对基于MSCs的自身免疫性疾病治疗的兴趣日益增加，这些结果具有转化相关性。
