Mattei M, Bach S, Di Cesare S, Fraziano M, Placido R, Poccia F, Sammarco I, Moras A M, Bardone M R, Colizzi V
CaveTech Animal Breeding Unit, Rome, Italy.
Int J Immunopharmacol. 1994 Aug;16(8):651-8. doi: 10.1016/0192-0561(94)90138-4.
The in vivo effect of thymic factors on immature lymphocytes was analysed in MRL/lpr mice. This strain carries a genetic defect that causes during their life cycle a block of T-cell differentiation and abnormal proliferation of CD4-8- (double-negative, DN) T-lymphocytes. In vivo administration of four preparations of thymic factors, thymopentin (TP-1), thymopoietin (TP-5), thymolymphotropin (TLT), and thymomodulin (TMD) into young (2-month-old) MRL/lpr mice induced a significant increase of DN T-cells both in the thymus and in the peripheral lymph nodes, with a concomitant decrease of double-positive (DP) T-cells in the thymus and of single-positive (SP) T-cells in the lymph nodes. The level of DNA fragmentation measured as propidium iodide fluorescence was increased in the thymus population of young mice and in the lymph node population of old mice treated with TLT. SCID mice transplanted with lymph node cells from MRL/lpr donors (MRL-->SCID) developed graft versus host (GvH) reaction due to the activation of MRL CD8+ alloreactive T-cells. This model was used to analyse the effect of TMD/TLT in vivo on MRL cell proliferation and expansion; in fact, spleen cells from MRL-->SCID mice after treatment with TMD/TLT showed an increased cell proliferation, and an expansion of DN T-cells with a concomitant decrease of SP cells (both CD4+ and CD8+ cells). Decreased SP cell numbers in this context could explain why TMD/TLT treatment of SCID mice engrafted with MRL cells increased their survival compared to untreated MRL-->SCID mice.
在MRL/lpr小鼠中分析了胸腺因子对未成熟淋巴细胞的体内作用。该品系携带一种遗传缺陷，导致在其生命周期中T细胞分化受阻以及CD4-8-（双阴性，DN）T淋巴细胞异常增殖。向年轻（2个月大）的MRL/lpr小鼠体内注射四种胸腺因子制剂，即胸腺五肽（TP-1）、胸腺生成素（TP-5）、胸腺淋巴细胞生成素（TLT）和胸腺调节素（TMD），可导致胸腺和外周淋巴结中DN T细胞显著增加，同时胸腺中双阳性（DP）T细胞和淋巴结中单阳性（SP）T细胞减少。以碘化丙啶荧光测量的DNA片段化水平在接受TLT治疗的年轻小鼠胸腺群体和老年小鼠淋巴结群体中有所增加。用来自MRL/lpr供体的淋巴结细胞移植的SCID小鼠（MRL→SCID）由于MRL CD8+同种反应性T细胞的激活而发生移植物抗宿主（GvH）反应。该模型用于分析TMD/TLT在体内对MRL细胞增殖和扩增的影响；事实上，用TMD/TLT处理后的MRL→SCID小鼠的脾细胞显示细胞增殖增加，DN T细胞扩增，同时SP细胞（CD4+和CD8+细胞）减少。在这种情况下，SP细胞数量减少可以解释为什么与未处理的MRL→SCID小鼠相比，用TMD/TLT处理植入MRL细胞的SCID小鼠可提高其存活率。
