Hanna E E, Hale M
Infect Immun. 1975 Feb;11(2):265-72. doi: 10.1128/iai.11.2.265-272.1975.
An unregulated, elevated rebound of antibody levels in rabbits was shown to follow late (10 to 15 days) after steptococcal pyrogenic exotoxin (SPE)-induced immunosuppression. Because of that result we have suggested that SPE acts by preferentially inhibiting a regulatory cell which normally limits the extent of full expression of antibody formation by B-cells. We are currently testing this hypothesis in mice. NIH (Swiss Webster) mice (+/+) or NIH (Swiss Webster) mice heterozygous (+/nu) for the mutant athymic nude gene and phenotypically normal showed an elevated plaque-forming cell (PFC) response to sheep erythrocytes (SE) late (10 to 15 days) after immunosuppressive SPE treatment similar to that described in rabbits. Homozygous nude mice (nu/nu) that are phenotypically athymic normally show a reduced early (4 day) PFC response to SE (a T-cell-dependent antigen) as compared with +/nu littermates or +/+ parent strain mice. This cryptic early 4-day response was improved by injection of purified endotoxin (a B-cell mitogen), but these relatively elevated nude PFC responses had decreased to normal control (SE only)nude PFC levels before 10 days. In similar SE-injected nude mice treated instead with SPE, no elevation at 4 days was observed and, more pertinently, the late (10 to 15 day) elevated rebound of PFC levels observed in normal response controls (+/nu or +/+) was not observed. Similar experiments were subsequently conducted in Marbrook-type spleen PFC cultures during periods of 12 days. The results of these experiments paralleled the in vivo results above, and in addition showed that SPE induced a large proliferation of either +/+ or +/nu cells (T-and B-cells) in culture but had no such effect on nu/nu cells (B-cells) in culture. Purified endotoxin, the Bcell mitogen, had a better sparing effect on nu/nu cells in this respect. These results are consistent with our premise that SPE inhibits preferentially the function of a regulator of the antibody response. The regulator appears to be a T-cell and is likely a suppressor T-cell.
已表明，在感染链球菌热原性外毒素（SPE）导致免疫抑制后较晚时间（10至15天），家兔体内会出现不受调控的抗体水平升高反弹。基于这一结果，我们提出SPE的作用机制是优先抑制一种调节细胞，这种调节细胞通常会限制B细胞抗体形成完全表达的程度。我们目前正在小鼠中验证这一假设。国立卫生研究院（瑞士韦伯斯特）野生型小鼠（+/+）或携带无胸腺裸基因杂合子（+/nu）且表型正常的国立卫生研究院（瑞士韦伯斯特）小鼠，在接受免疫抑制性SPE治疗后较晚时间（10至15天），对绵羊红细胞（SE）的空斑形成细胞（PFC）反应升高，这与在家兔中描述的情况相似。表型无胸腺的纯合子裸鼠（nu/nu），与+/nu同窝小鼠或+/+亲本品系小鼠相比，通常对SE（一种T细胞依赖性抗原）的早期（4天）PFC反应降低。通过注射纯化的内毒素（一种B细胞有丝分裂原）可改善这种隐匿的早期4天反应，但这些相对升高的裸鼠PFC反应在10天前已降至正常对照（仅SE）裸鼠PFC水平。在用SPE替代治疗的类似SE注射裸鼠中，未观察到4天时的升高，更相关的是，未观察到在正常反应对照组（+/nu或+/+）中观察到的PFC水平在后期（10至15天）的升高反弹。随后在12天期间在马尔布鲁克型脾PFC培养物中进行了类似实验。这些实验结果与上述体内实验结果相似，此外还表明，SPE在培养物中可诱导+/+或+/nu细胞（T细胞和B细胞）大量增殖，但对培养物中的nu/nu细胞（B细胞）无此作用。在这方面，纯化的内毒素，即B细胞有丝分裂原，对nu/nu细胞具有更好的保护作用。这些结果与我们的假设一致，即SPE优先抑制抗体反应调节因子的功能。该调节因子似乎是一种T细胞，很可能是抑制性T细胞。
