Schulze-Koops H, Lipsky P E, Davis L S
University of Texas Southwestern Medical Center, Department of Internal Medicine, Dallas 75235-8884, USA.
Eur J Immunol. 1998 Aug;28(8):2517-29. doi: 10.1002/(SICI)1521-4141(199808)28:08<2517::AID-IMMU2517>3.0.CO;2-5.
Freshly isolated memory T cells primarily produced IL-2 and small amounts of IL-4 and IFN-gamma after stimulation in vitro. Priming for 5 days in vitro with anti-CD28 monoclonal antibodies (mAb) alone markedly increased production of IL-4. In comparison to fresh cells, the increase in the amount of IL-4 secreted reflected a marked increase in the number of IL-4-producing cells. Stimulation with immobilized anti-CD3 mAb during priming limited subsequent IL-4 production. By contrast, IFN-gamma production from in vitro primed memory T cells was directly correlated to the concentration of priming anti-CD3 mAb. IL-2 production by all restimulated cells was decreased. The differentiation of IL-4-producing cells could be blocked by antibody to IL-4 and enhanced by the addition of recombinant IL-4 as well as antibody to IFN-gamma. Of note, the IL-4-producing effector cells induced from in vitro priming derived from the early CD27pos memory T cell subset, whereas the small CD27neg differentiated memory subset produced IL-4 without in vitro priming. The results indicate that memory T cells can be directed to differentiate into IL-4-producing effector cells by stimulation via CD28 and IL-4, whereas increasing engagement of the TCR limits Th2 memory cell differentiation.
新鲜分离的记忆T细胞在体外刺激后主要产生IL-2以及少量的IL-4和IFN-γ。单独用抗CD28单克隆抗体（mAb）在体外预刺激5天可显著增加IL-4的产生。与新鲜细胞相比，IL-4分泌量的增加反映了产生IL-4的细胞数量显著增加。预刺激期间用固定化抗CD3 mAb刺激会限制随后的IL-4产生。相比之下，体外预刺激的记忆T细胞产生的IFN-γ与预刺激抗CD3 mAb的浓度直接相关。所有再次刺激的细胞产生的IL-2均减少。产生IL-4的细胞的分化可被抗IL-4抗体阻断，并通过添加重组IL-4以及抗IFN-γ抗体增强。值得注意的是，体外预刺激诱导产生IL-4的效应细胞来源于早期CD27阳性记忆T细胞亚群，而小的CD27阴性分化记忆亚群在没有体外预刺激的情况下产生IL-4。结果表明，记忆T细胞可通过经由CD28和IL-4的刺激被引导分化为产生IL-4的效应细胞，而TCR参与度的增加会限制Th2记忆细胞的分化。
