Bell S J, Buxser S E
Section of Allergy/Immunology, East Carolina University School of Medicine, Greenville, North Carolina 27858.
Cell Immunol. 1995 Jan;160(1):58-64. doi: 10.1016/0008-8749(95)80009-8.
Primary in vivo challenge with the superantigen staphylococcal enterotoxin B (SEB) induces polyclonal proliferation of an unusually large proportion of circulating T-cells that bear the V beta 8-T-cell receptor (TcR) domain. Early and vigorous proliferation of V beta 8+ T-cells precedes their selective deletion, leaving the host unresponsive upon rechallenge with the native immunogen SEB. Nonetheless, this induction of anergy is incompletely understood. Recently we demonstrated that more cells than just V beta 8+ T-cells undergo clonal proliferation after challenge with SEB (Cell. Immunol. 154, 440, 1994). These findings suggested that non-V beta 8+ T-cells may have a role in the induction of superantigen-induced anergy. To further investigate this, we enumerated CD4+ and CD8+ T-cells in lymph nodes and spleens from Balb/c mice at various times after primary and secondary challenge with either a high or a low dose of SEB. Using these kinetic data we investigated whether challenge with SEB would modulate antigen-specific V beta 8-associated T-memory responses. To this end, the V beta 8+ T-cell-associated responses induced by SEB were compared with the V beta 8+ TcR-associated memory responses induced by the nominal antigen sperm whale myoglobin (SWM). Results indicated that challenge of SWM-primed mice with SEB abrogated the V beta 8-associated SWM-specific T-cell memory for an extended but transient period of time. Moreover, prechallenge with SEB blocked the establishment of de novo V beta + T-cell-mediated immunity. These findings suggest that administration of low and controlled doses of microbial superantigen could provide long-term suppression of antigen-specific cell-mediated immunity.
用超抗原葡萄球菌肠毒素B（SEB）进行初次体内攻击可诱导大量携带Vβ8 - T细胞受体（TcR）结构域的循环T细胞发生多克隆增殖。Vβ8 + T细胞的早期强烈增殖先于其选择性缺失，使得宿主在用天然免疫原SEB再次攻击时无反应。然而，这种无反应性的诱导机制尚未完全明确。最近我们证明，在用SEB攻击后，发生克隆增殖的细胞不止Vβ8 + T细胞（《细胞免疫学》154, 440, 1994）。这些发现表明非Vβ8 + T细胞可能在超抗原诱导的无反应性诱导中起作用。为进一步研究此问题，我们在高剂量或低剂量SEB初次和二次攻击后的不同时间，对Balb/c小鼠淋巴结和脾脏中的CD4 +和CD8 + T细胞进行了计数。利用这些动力学数据，我们研究了用SEB攻击是否会调节抗原特异性Vβ8相关的T记忆反应。为此，将SEB诱导的Vβ8 + T细胞相关反应与名义抗原抹香鲸肌红蛋白（SWM）诱导的Vβ8 + TcR相关记忆反应进行了比较。结果表明，用SEB攻击经SWM致敏的小鼠会在一段延长但短暂的时间内消除Vβ8相关的SWM特异性T细胞记忆。此外，用SEB预攻击会阻断新生Vβ + T细胞介导的免疫的建立。这些发现表明，给予低剂量且可控的微生物超抗原可长期抑制抗原特异性细胞介导的免疫。
