Kemp Roslyn A, Bäckström B Thomas, Ronchese Franca
Malaghan Institute of Medical Research, Wellington, New Zealand.
Immunology. 2005 Jul;115(3):315-24. doi: 10.1111/j.1365-2567.2005.02168.x.
We used various culture conditions to generate type 1 (Tc1) or type 2 (Tc2) cytotoxic T cells in vitro. T-cell receptor (TCR) transgenic T cells were cultured with antigen and spleen cells, or antigen and dendritic cells (DC), or anti-CD3 and anti-CD28. Tc1 cultures contained interleukin (IL)-2 and IL-6, and Tc2 cultures contained IL-2, IL-6 and IL-4. Tc2 cells generated in each culture condition acquired a CD62L(low) CD44(high) phenotype, had high cytotoxic activity, and secreted IL-4, IL-5 and moderate amounts of interferon-gamma (IFN-gamma). In contrast, the phenotype and function of Tc1 cells varied depending on culture conditions. Tc1 cells from anti-CD3 and anti-CD28 cultures had high cytotoxic activity and were CD62L(low) CD44(high), while Tc1 cells from antigen and spleen cell cultures had low cytotoxic activity and were CD62L(high) CD44(low). Tc1 cells from antigen and DC cultures had an intermediate phenotype. All Tc1 cells secreted high amounts of IFN-gamma, but only Tc1 from anti-CD3 and anti-CD28 cultures had antitumour activity in vivo. Differences were not caused by suboptimal culture conditions, as Tc1 cells divided at a similar rate whether cultured with antigen and spleen cells or with anti-CD3 and anti-CD28. We conclude that IL-4 not only induces 'type 2' cytokine secretion in CD8(+) T cells, but also affects their expression of surface markers and cytotoxic activity.
我们采用多种培养条件在体外生成1型（Tc1）或2型（Tc2）细胞毒性T细胞。将T细胞受体（TCR）转基因T细胞与抗原和脾细胞、或抗原和树突状细胞（DC）、或抗CD3和抗CD28一起培养。Tc1培养物中含有白细胞介素（IL）-2和IL-6，而Tc2培养物中含有IL-2、IL-6和IL-4。在每种培养条件下生成的Tc2细胞获得CD62L（低）CD44（高）表型，具有高细胞毒性活性，并分泌IL-4、IL-5和适量的干扰素-γ（IFN-γ）。相比之下，Tc1细胞的表型和功能因培养条件而异。来自抗CD3和抗CD28培养物的Tc1细胞具有高细胞毒性活性，为CD62L（低）CD44（高），而来自抗原和脾细胞培养物的Tc1细胞具有低细胞毒性活性，为CD62L（高）CD44（低）。来自抗原和DC培养物的Tc1细胞具有中间表型。所有Tc1细胞均分泌大量的IFN-γ，但只有来自抗CD3和抗CD28培养物的Tc1细胞在体内具有抗肿瘤活性。差异并非由次优培养条件引起，因为无论与抗原和脾细胞一起培养还是与抗CD3和抗CD28一起培养，Tc1细胞的分裂速率相似。我们得出结论，IL-4不仅诱导CD8（+）T细胞分泌“2型”细胞因子，还影响其表面标志物的表达和细胞毒性活性。
