Dhaliwal J S, Liew F Y
Infect Immun. 1987 Mar;55(3):645-51. doi: 10.1128/iai.55.3.645-651.1987.
BALB/c mice injected intradermally with 10(5) or higher doses of formaldehyde-fixed promastigotes (FFP) of Leishmania major developed strong delayed-type hypersensitivity (DTH) to leishmanial antigens injected into the hind footpad 3 to 10 days later. The DTH peaked 15 to 18 h after footpad injection and disappeared by 48 h. This specific DTH correlated with the homing of 51Cr-labeled syngeneic bone marrow cells and the infiltration of proliferating cells to the site of antigen administration. Spleen cells from FFP-sensitized mice also gave significant proliferative response to FFP in vitro. The DTH was adoptively transferable by Lyt-1+2-L3T4+ T cells and was H-2 restricted. DTH could be substantially enhanced by pretreatment with cyclophosphamide or pertussigen. Such DTH enhancement was accompanied by concomitant exacerbation of disease progression after L. major infection. Mice injected intravenously with FFP developed substantial immunity to cutaneous leishmaniasis but specifically suppressed DTH reactivity. Treatment of mice with pertussigen before intravenous immunization, however, abolished the protection and reversed the suppression of DTH. These results therefore demonstrate that the early-appearing type of DTH is not involved in host protection but that it actually facilitates disease progression in cutaneous leishmaniasis. Further evidence, which also shows the nonspecific nature of this disease exacerbation, is provided by local cell transfer experiments. Splenic T cells from mice sensitized to keyhole limpet hemocyanin or FFP induced significantly larger lesions compared with normal T cells when they were transferred into the footpad together with specific antigen and L. major promastigotes.
给BALB/c小鼠皮内注射10⁵或更高剂量的利什曼原虫主要亚种甲醛固定前鞭毛体（FFP），3至10天后，小鼠对注射到后足垫的利什曼原虫抗原产生强烈的迟发型超敏反应（DTH）。DTH在足垫注射后15至18小时达到峰值，并在48小时后消失。这种特异性DTH与⁵¹Cr标记的同基因骨髓细胞归巢以及增殖细胞向抗原给药部位的浸润相关。FFP致敏小鼠的脾细胞在体外对FFP也有显著的增殖反应。DTH可由Lyt-1⁺2⁻L3T4⁺T细胞进行过继转移，且受H-2限制。用环磷酰胺或百日咳杆菌毒素预处理可显著增强DTH。这种DTH增强伴随着利什曼原虫主要亚种感染后疾病进展的加剧。静脉注射FFP的小鼠对皮肤利什曼病产生了显著的免疫力，但特异性地抑制了DTH反应性。然而，在静脉免疫前用百日咳杆菌毒素治疗小鼠，可消除保护作用并逆转DTH的抑制。因此，这些结果表明，早期出现的DTH类型不参与宿主保护，实际上它促进了皮肤利什曼病的疾病进展。局部细胞转移实验提供了进一步的证据，也表明了这种疾病加剧的非特异性性质。当将对钥孔戚血蓝蛋白或FFP致敏的小鼠的脾T细胞与特异性抗原和利什曼原虫主要亚种前鞭毛体一起转移到足垫时，与正常T细胞相比，它们诱导的病变明显更大。
