Aloisi F, Ria F, Columba-Cabezas S, Hess H, Penna G, Adorini L
Laboratory of Organ and System Pathophysiology, Istituto Superiore di Sanità, Roma, Italy.
Eur J Immunol. 1999 Sep;29(9):2705-14. doi: 10.1002/(SICI)1521-4141(199909)29:09<2705::AID-IMMU2705>3.0.CO;2-1.
We have compared the efficiency of central nervous system and peripheral antigen-presenting cells (APC) in T cell priming and restimulation. OVA peptide 323 - 339-dependent activation of DO11.10 TCR-transgenic naive CD4+ and polarized Th1 or Th2 cells was assessed in the presence of microglia and astrocytes from the neonatal mouse brain as well as dendritic cells (DC) and B cells purified from adult mouse lymph nodes. DC were the most efficient in inducing naive T cell proliferation, IL-2 secretion and differentiation into Th1 cells, followed by IFN-gamma-preactivated microglia, large and small B cells. Astrocytes failed to activate naive T cells. IFN-gamma-pretreated microglia were as efficient as DC in the restimulation of Th1 cells, whereas IFN-gamma-pretreated astrocytes, large and small B cells were much less efficient. Conversely, Th2 cells were efficiently restimulated by all the APC types examined. During T cell priming, DC secreted more IL-12 than microglia but similar amounts of IL-12 were secreted by the two cell types upon interaction with Th1 cells. The hierarchy of APC established in this study indicates that DC and microglia are the most efficient in the stimulation of naive CD4(+) T cells and in the restimulation of Th1 cells, suggesting that activated microglia may effectively contribute to Th1 responses leading to central nervous system inflammation and tissue damage. These potentially pathogenic responses could be counteracted by the high efficiency of astrocytes as well as microglia in restimulating Th2 cells.
我们比较了中枢神经系统和外周抗原呈递细胞（APC）在T细胞致敏和再刺激中的效率。在存在来自新生小鼠脑的小胶质细胞和星形胶质细胞以及从成年小鼠淋巴结纯化的树突状细胞（DC）和B细胞的情况下，评估了OVA肽323 - 339依赖性激活DO11.10 TCR转基因幼稚CD4 +以及极化的Th1或Th2细胞。DC在诱导幼稚T细胞增殖、IL-2分泌和分化为Th1细胞方面效率最高，其次是IFN-γ预激活的小胶质细胞、大B细胞和小B细胞。星形胶质细胞未能激活幼稚T细胞。IFN-γ预处理的小胶质细胞在Th1细胞的再刺激方面与DC一样有效，而IFN-γ预处理的星形胶质细胞、大B细胞和小B细胞效率则低得多。相反，所有检测的APC类型都能有效地再刺激Th2细胞。在T细胞致敏过程中，DC分泌的IL-12比小胶质细胞多，但与Th1细胞相互作用时，这两种细胞类型分泌的IL-12量相似。本研究中确立的APC等级表明，DC和小胶质细胞在刺激幼稚CD4(+) T细胞和再刺激Th1细胞方面效率最高，这表明活化的小胶质细胞可能有效地促进导致中枢神经系统炎症和组织损伤的Th1反应。星形胶质细胞以及小胶质细胞在再刺激Th2细胞方面的高效率可能会抵消这些潜在的致病反应。
