Department of Internal Medicine, University of Missouri, One Hospital Drive, Med Sci M307, Columbia, MO 65212, USA.
Cell Immunol. 2013 Sep-Oct;285(1-2):84-91. doi: 10.1016/j.cellimm.2013.09.003. Epub 2013 Sep 18.
IFN-γ(-/-) NOD.H-2h4 mice develop a spontaneous autoimmune thyroid disease, thyroid epithelial cell hyperplasia and proliferation (TEC H/P) when given NaI in their water for 7+ mo. TEC H/P can be transferred to IFN-γ(-/-) SCID mice by splenocytes from mice with severe (4-5+) disease, and transfer of TEC H/P is improved when splenocytes are cultured prior to transfer. Older (9+ mo) IFN-γ(-/-) NOD.H-2h4 mice have elevated numbers of FoxP3(+) T reg cells, up to 2-fold greater than younger (2 mo) mice. During culture, the number of T reg decreases and this allows the improved transfer of TEC H/P. Co-culture with IL-2 prior to transfer prevents the decrease of T reg and improves their in vitro suppressive ability resulting in reduced TEC H/P in recipient mice. Therefore, culturing splenocytes improves transfer of TEC H/P by reducing the number of T reg and IL-2 inhibits transfer by preserving T reg number and function.
IFN-γ(-/-) NOD.H-2h4 小鼠在饮水中给予碘化钠 7 个月以上时,会发展出自发性自身免疫性甲状腺疾病、甲状腺上皮细胞增生和增殖(TEC H/P)。严重(4-5+)疾病小鼠的脾细胞可将 TEC H/P 转移至 IFN-γ(-/-) SCID 小鼠,且脾细胞在转移前培养可提高 TEC H/P 的转移效率。年龄较大(9 个月以上)的 IFN-γ(-/-) NOD.H-2h4 小鼠的 FoxP3(+) Treg 细胞数量增加,高达年轻(2 个月)小鼠的两倍。在培养过程中,Treg 细胞的数量减少,从而提高了 TEC H/P 的转移效率。转移前与 IL-2 共培养可防止 Treg 细胞数量减少,并提高其体外抑制能力,从而使受体小鼠中的 TEC H/P 减少。因此,培养脾细胞可通过减少 Treg 细胞的数量来提高 TEC H/P 的转移效率,而 IL-2 通过维持 Treg 细胞的数量和功能来抑制转移。