Brenden N, Böhme J
Department of Immunology, Wenner-Gren Institute, Arrhenius Laboratories for Natural Sciences, Stockholm University, S-106 91 Stockholm, Sweden.
Immunogenetics. 1999 Jan;49(1):1-6. doi: 10.1007/s002510050457.
Positive selection has been proposed to be involved in protection from diabetes. We examined positive selection by fluorescence-activated cell sorter analyses in thymocytes of protected and susceptible E-transgenic and non-transgenic NOD mice. Three Vb families showed positive selection in E-transgenic mice. Vb6(+)CD4(+) and Vb10(+)CD4(+) thymocytes were found at higher frequencies in both protected NOD-Ea and susceptible NOD-DY mice. The increased frequencies of Vb13(+)CD8(+) thymocytes were found in protected NOD-Ea mice only, and not in susceptible NOD-DY transgenic mice. These three Vb families were further examined in bone-marrow chimeras between NOD-Ea and non-transgenic NOD mice, where we could examine the contribution of E-expressing bone-marrow-derived cells in positive selection. We find that NOD-Ea-->NOD-Ea chimeras have an increased positive selection of Vb13(+)CD8(+) cells and that positive selection is more efficient when both thymic epithelium and bone-marrow-derived cells express the E molecule. This was also seen for Vb6(+)CD4(+) cells. However, for Vb6, bone-marrow-derived cells alone were also capable of positive selection. Positive selection of Vb10(+)CD4(+) cells was restricted to E-expressing thymic epithelium only. For Vb13(+)CD8(+ )cells, we found that positive selection is most efficient with E-expression on both thymic epithelium and bone-marrow-derived cells, although positive selection also occurs with E-positive epithelium only. For Vb6(+) CD4(+) cells, the dominating selecting cells are bone-marrow-derived cells, and Vb10(+)CD4(+ )cells seem to be selected exclusively by the thymic epithelium. Thus, the conditions for positive selection seem to vary considerably between different Vb families.
有人提出正向选择参与了对糖尿病的保护作用。我们通过荧光激活细胞分选分析，在受保护的和易患糖尿病的E转基因及非转基因NOD小鼠的胸腺细胞中检测正向选择。三个Vb家族在E转基因小鼠中表现出正向选择。在受保护的NOD-Ea小鼠和易患糖尿病的NOD-DY小鼠中，Vb6(+)CD4(+)和Vb10(+)CD4(+)胸腺细胞的频率都较高。仅在受保护的NOD-Ea小鼠中发现Vb13(+)CD8(+)胸腺细胞的频率增加，而在易患糖尿病的NOD-DY转基因小鼠中未发现。在NOD-Ea和非转基因NOD小鼠之间的骨髓嵌合体中进一步研究了这三个Vb家族，在那里我们可以检测表达E的骨髓来源细胞在正向选择中的作用。我们发现NOD-Ea→NOD-Ea嵌合体中Vb13(+)CD8(+)细胞的正向选择增加，并且当胸腺上皮和骨髓来源细胞都表达E分子时，正向选择更有效。Vb6(+)CD4(+)细胞也观察到这种情况。然而，对于Vb6，仅骨髓来源细胞也能够进行正向选择。Vb10(+)CD4(+)细胞的正向选择仅限于仅表达E的胸腺上皮。对于Vb13(+)CD8(+)细胞，我们发现当胸腺上皮和骨髓来源细胞都表达E时，正向选择最有效，尽管仅E阳性上皮也会发生正向选择。对于Vb6(+)CD4(+)细胞，主要的选择细胞是骨髓来源细胞，而Vb10(+)CD4(+)细胞似乎仅由胸腺上皮选择。因此，不同Vb家族之间正向选择的条件似乎有很大差异。
