Immunological regulation of experimental cutaneous leishmaniasis. IV. Prophylactic effect of sublethal irradiation as a result of abrogation of suppressor T cell generation in mice genetically susceptible to Leishmania tropica.
Immunological regulation of experimental cutaneous leishmaniasis. IV. Prophylactic effect of sublethal irradiation as a result of abrogation of suppressor T cell generation in mice genetically susceptible to Leishmania tropica.
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DOI：
10.1084/jem.153.3.557
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发表时间：
1981-03-01
影响因子：
15.3
通讯作者：
Liew, F Y
中科院分区：
文献类型：
--
作者：
Howard, J G;Hale, C;Liew, F Y
BALB/c小鼠对热带利什曼原虫感染具有极高的易感性，这种易感性可通过紧接在感染前进行亚致死剂量照射而得到显著逆转。这与辐射剂量有关，在550拉德时，可使60%的小鼠完全治愈，且进行性疾病的发病率仅为19%（而非100%）。感染前10天进行照射仅有微弱的预防作用，而感染后10天照射则无效果。病变发展的控制在最初30天后才明显，这与之前在抗性品系以及成年胸腺切除、X射线照射、骨髓重建的BALB/c小鼠中发现的类似发病情况相吻合。经照射治愈的小鼠没有出现BALB/c品系热带利什曼原虫感染所特有的迟发型超敏反应（DTH）的特异性抑制，而是表现出强烈的抗利什曼原虫的DTH反应性以及对再感染的抵抗力。来自这些小鼠的T细胞可转移DTH反应性，这种反应性会因与未治愈、无反应的供体的细胞混合而被抑制。经照射的BALB/c小鼠在疾病暂时停止进展后，当用正常T细胞进行重建时，又会不可避免地出现疾病进展。当T细胞来自无法控制感染的供体时，其恢复的易感性与正常小鼠无异。B细胞不会改变550拉德的预防效果，而来自治愈小鼠的T细胞在初始阶段可提供强大的保护性免疫。在所有这些组中，疾病的消退或进展与DTH反应性完全相关。尽管BALB/c小鼠对热带利什曼原虫感染表现出极高的遗传易感性，但它们仍然能够产生一种具有治疗作用的细胞介导的免疫反应。之前认为在疾病发病过程中这种免疫反应无效与强效的特异性抑制性T细胞的产生相关，现在表明这种情况可通过预先照射来预防。然而，最重要的是，通过重建已直接证明了这些细胞在体内的致病作用。
The overwhelming susceptibility of BALB/c mice to infection with Leishmania tropica can be substantially reversed by immediately prior sub-lethal irradiation. This is related to radiation dosage, and at 550 rad, causes 60 percent complete cures and only 19 percent (instead of 100 percent) incidence of progressive disease. Irradiation 10 d before infection is only weakly prophylactic, whereas 10 d after is without effect. Control of lesion development is only apparent after the first 30 d, coincident with the analogous onset previously found in resistant strains and adult thymectomized, x-irradiated, bone marrow-reconstituted BALB/c mice. Instead of the specific suppression of DTH characteristic of L. tropica infection in the BALB/c strain, healed irradiated mice express strong anti-leishmanial DTH reactivity and resistance to reinfection. T cells from these mice transfer DTH reactivity which is suppressed by admixture with cells from nonhealed, nonreactive donors. Irradiated BALB/c mice again develop inexorable disease progression, after its transient arrest, when they are reconstituted with normal T cells. When the T cells are derived from uncontrollably-infected donors, the susceptibility regained is indistinguishable from that of normal mice. B cells do not modify the prophylactic effect of 550 rad, whereas T cells from healed mice confer strong protective immunity throughout the initial phase. Regression or progression of disease correlates completely with DTH reactivity in all these groups. Although BALB/c mice express an extreme level of genetic susceptibility to L. tropica infection, they are nevertheless capable of mounting a curative cell mediated immune response. That this is ineffective during pathogenesis of the disease was previously associated correlatively with potent specific suppressor T cell generation, which is now shown to be preventable by prior irradiation. Most important, however, a causal role for these cells in vivo has been demonstrated directly by reconstitution.