Schmid D S, Rouse B T
J Immunol. 1983 Jul;131(1):479-84.
The role and induction requirements of helper T lymphocyte responses to herpes simplex virus type 1 (HSV-1) was examined. Splenocytes from mice that had been primed in vivo with infectious HSV-1 can be restimulated in vitro with live or partially UV-inactivated HSV-1 to generate high levels of herpes virus-specific cytotoxic T lymphocyte (CTL) activity. By comparison, naive splenocytes or splenocytes taken from mice primed with heat-inactivated HSV-1 failed to generate CTL after in vitro viral stimulation. In addition, infectious HSV-primed splenocytes can be rendered unresponsive to secondary in vitro restimulation by pretreatment with anti-Lyt-1 antiserum plus complement. Spleen cells were taken from mice that had been primed and restimulated in vivo with infectious HSV-1. Two days after the second priming, splenocytes were prepared and irradiated. These cells were capable of assisting in the generation of CTL to varying degrees in all of the above unresponsive populations of cells. The irradiated cells did not produce detectable levels of CTL activity when cultured alone with antigen. Also, if the irradiated splenocytes were treated with anti-Lyt-1 plus complement before their addition to cultures, all restorative activity was ablated. In contrast, irradiated splenocytes from mice that had been primed and restimulated in vivo with either heat-inactivated or UV-inactivated HSV-1 were unable to provide help to naive or helper-depleted cultures. The failure to supply helper activity appears not to involve the preferential activation of suppressor cells, as evidenced by cell mixing experiments and the addition of concentrated, antigen-stimulated spleen cell supernatant fluids to secondary anti-HSV-1 splenocyte cultures. Proliferative assays using interleukin 2- (IL 2) dependent cell lines as a measure of relative helper activity indicated that the inactivated forms of HSV-1 were incapable of effectively enlisting helper activity. These experiments therefore suggest that the observed failure of heat-inactivated or UV-inactivated HSV-1 preparations to induce anti-HSV CTL responses reflects the inability of the HSV-1-specific subset of helper T lymphocytes to recognize these forms of the antigen.
研究了辅助性T淋巴细胞对1型单纯疱疹病毒（HSV-1）应答的作用及诱导条件。用感染性HSV-1在体内进行过初次免疫的小鼠脾细胞，可在体外被活的或部分紫外线灭活的HSV-1再次刺激，从而产生高水平的疱疹病毒特异性细胞毒性T淋巴细胞（CTL）活性。相比之下，未经免疫的脾细胞或用热灭活HSV-1免疫的小鼠脾细胞，在体外病毒刺激后无法产生CTL。此外，用抗Lyt-1抗血清加补体预处理感染性HSV初次免疫的脾细胞，可使其对二次体外再刺激无反应。从用感染性HSV-1在体内进行过初次免疫和再次刺激的小鼠中获取脾细胞。第二次初次免疫两天后，制备脾细胞并进行辐照。这些细胞能够在不同程度上协助上述所有无反应性细胞群体产生CTL。辐照后的细胞单独与抗原培养时，不会产生可检测水平的CTL活性。此外，如果在将辐照后的脾细胞加入培养物之前，先用抗Lyt-1加补体处理，所有恢复活性都会被消除。相比之下，用热灭活或紫外线灭活的HSV-1在体内进行过初次免疫和再次刺激的小鼠的辐照脾细胞，无法为未经免疫或辅助性T细胞缺失的培养物提供帮助。细胞混合实验以及向二次抗HSV-1脾细胞培养物中添加浓缩的、抗原刺激的脾细胞上清液表明，未能提供辅助活性似乎并不涉及抑制性细胞的优先激活。使用依赖白细胞介素2（IL-2）的细胞系进行增殖测定以衡量相对辅助活性，结果表明HSV-1的灭活形式无法有效募集辅助活性。因此，这些实验表明，观察到热灭活或紫外线灭活的HSV-1制剂无法诱导抗HSV CTL应答，反映出辅助性T淋巴细胞的HSV-1特异性亚群无法识别这些形式的抗原。
