Thomsen A R, Marker O
Scand J Immunol. 1986 Aug;24(2):137-45. doi: 10.1111/j.1365-3083.1986.tb02079.x.
An increase in the virus dose from 10(2) LD50 (low dose) to 10(4) LD50 (high dose) of lymphocytic choriomeningitis virus (LCMV) results in markedly delayed virus clearance, in spite of a potent cytotoxic T-cell (TC) response. However, virus-specific delayed-type hypersensitivity (DTH) reactivity is markedly depressed in high-dose mice, suggesting an association between DTH and virus clearance. When virus-primed memory cells are transferred, DTH reactivity as well as virus-clearing capacity is restored in high-dose mice, indicating that the virus is not present in a changed or concealed form. The role of T-cells mediating DTH (TD cells) in virus clearance was also studied by adoptive transfer to naive recipients. Here the high-dose primed cells did mediate virus clearance, although no DTH reaction was detectable 24-72 h after transfer. However, when footpad swelling was measured 96 h or more after transfer a DTH response emerged, indicating that TD priming had taken place in high-dose animals. Pre-irradiation of high-dose primed cells markedly inhibited the antiviral activity as well as DTH, suggesting that upon transfer to naive recipients TD precursors from high-dose mice would proliferate into effector cells capable of mediating both functions. Treatment with anti-Lyt2+C' abrogated the capacity to induce virus-specific DTH, thus confirming that the cells involved are not helper T (TH) cells. We conclude that the DTH unresponsiveness in high-dose mice reflects a defective differentiation of TD precursor into effector cells which is reversible upon transfer to a less antigen loaded environment. Furthermore, it is suggested that TD function is crucial to the process of virus clearance.
将淋巴细胞性脉络丛脑膜炎病毒（LCMV）的病毒剂量从10（2）半数致死剂量（低剂量）增加到10（4）半数致死剂量（高剂量），尽管有强大的细胞毒性T细胞（TC）反应，但病毒清除明显延迟。然而，高剂量小鼠的病毒特异性迟发型超敏反应（DTH）反应明显受到抑制，这表明DTH与病毒清除之间存在关联。当转移经病毒致敏的记忆细胞时，高剂量小鼠的DTH反应性以及病毒清除能力得以恢复，这表明病毒并非以改变或隐匿的形式存在。通过将细胞过继转移给未致敏的受体，还研究了介导DTH的T细胞（TD细胞）在病毒清除中的作用。在此，高剂量致敏细胞确实介导了病毒清除，尽管在转移后24 - 72小时未检测到DTH反应。然而，当在转移后96小时或更长时间测量足垫肿胀时，出现了DTH反应，这表明在高剂量动物中发生了TD致敏。对高剂量致敏细胞进行预照射可显著抑制抗病毒活性以及DTH，这表明当转移到未致敏受体时，来自高剂量小鼠的TD前体细胞会增殖为能够介导这两种功能的效应细胞。用抗Lyt2 + C'抗体处理可消除诱导病毒特异性DTH的能力，从而证实所涉及的细胞不是辅助性T（TH）细胞。我们得出结论，高剂量小鼠中的DTH无反应性反映了TD前体向效应细胞的分化缺陷，这种缺陷在转移到抗原负载较少的环境中时是可逆的。此外，提示TD功能对病毒清除过程至关重要。
