Roth S, Dröge W
Cell Immunol. 1987 Sep;108(2):417-24. doi: 10.1016/0008-8749(87)90224-3.
Activated macrophages are known to release a variety of immunoregulatory substances including the low-molecular-weight substances hydrogen peroxide and lactate. We report here that lactate but not hydrogen peroxide is capable of supporting a substantial production of T-cell growth factor (TCGF) in cultures of accessory cell-depleted splenic T-cell populations after stimulation with concanavalin A. Hydrogen peroxide and its biosynthetic precursor superoxide anion (O2-) mediate, however, a strong augmentation of the TCGF production by accessory cell-depleted T-cell populations in the presence of lactate. Lactate inhibits the incorporation of [3H]thymidine in short-term cultures (18-26 hr) of accessory cell-depleted T cells. This confirms the rule that (optimal) production of T-cell growth factor requires a growth inhibitory signal. Concentrations of hydrogen peroxide which augment TCGF production most effectively (i.e., 1 X 10(-5) M) do not inhibit the incorporation of [3H]thymidine; and higher concentrations (3 X 10(-5)-1 X 10(-4) M) of hydrogen peroxide inhibit both the production of TCGF and the incorporation of [3H]thymidine. In agreement with the augmenting effect of hydrogen peroxide on TCGF production, it was observed that the proliferative response in mixed lymphocyte cultures is suppressed by catalase and augmented by 1 X 10(-5) M H2O2. Proliferative and cytotoxic responses in mixed lymphocyte cultures with an external source of interleukin 2 (IL-2) in contrast, are not augmented by 1 X 10(-5) M H2O2. The relatively high concentration of 1 X 10(-4) M hydrogen peroxide was found to inhibit the proliferative responses in mixed lymphocyte cultures with or without external IL-2 but not the cytotoxic response in the presence of IL-2. This indicates that CTL precursor cells may be relatively resistant against H2O2.
已知活化的巨噬细胞会释放多种免疫调节物质，包括低分子量物质过氧化氢和乳酸。我们在此报告，在用伴刀豆球蛋白A刺激后，在去除辅助细胞的脾T细胞群体培养物中，乳酸而非过氧化氢能够支持大量产生T细胞生长因子（TCGF）。然而，过氧化氢及其生物合成前体超氧阴离子（O2-）在乳酸存在的情况下，可介导去除辅助细胞的T细胞群体对TCGF产生的强烈增强作用。乳酸会抑制去除辅助细胞的T细胞短期培养（18 - 26小时）中[3H]胸苷的掺入。这证实了T细胞生长因子（最佳）产生需要生长抑制信号这一规律。最有效地增强TCGF产生的过氧化氢浓度（即1×10^(-5) M）不会抑制[3H]胸苷的掺入；而更高浓度（3×10^(-5) - 1×10^(-4) M）的过氧化氢则会抑制TCGF的产生以及[3H]胸苷的掺入。与过氧化氢对TCGF产生的增强作用一致，观察到在混合淋巴细胞培养中，过氧化氢酶会抑制增殖反应，而1×10^(-5) M H2O2会增强增殖反应。相比之下，在有外源性白细胞介素2（IL - 2）的混合淋巴细胞培养中，增殖和细胞毒性反应不会被1×10^(-5) M H2O2增强。发现相对较高浓度的1×10^(-4) M过氧化氢会抑制有或无外源性IL - 2的混合淋巴细胞培养中的增殖反应，但不会抑制有IL - 2存在时的细胞毒性反应。这表明细胞毒性T淋巴细胞前体细胞可能对H2O2相对耐药。
