Prina E, Lang T, Glaichenhaus N, Antoine J C
Unit of Cellular Immunophysiology, Pasteur Institute, Paris, France.
J Immunol. 1996 Jun 1;156(11):4318-27.
Macrophages are apparently the only cells that in vivo allow the growth of the intracellular pathogen Leishmania. They are thus generally considered as likely candidates for the presentation of parasite Ag to CD4+ T lymphocytes known to be involved in protective and counterprotective immune responses. In the present study, we examined whether mouse macrophages infected with Leishmania were capable of stimulating T cell hybrids and a T cell clone reacting with the previously identified protective Ag LACK (Leishmania homologue of receptors for Activated C Kinase). This parasite protein is expressed in both promastigote and amastigote stages of Leishmania. We found that IFN-gamma-treated macrophages recently infected with live Leishmania promastigotes were fully competent to activate LACK-reactive T cells. However, at later times of infection, permissive macrophages infected with promastigotes were no longer able to present LACK, in spite of the presence of numerous intracellular parasites. This punctual presentation of LACK was apparently linked with the destruction, at least partial, of the intracellular parasites. In contrast, macrophages infected with live Leishmania amastigotes were always unable to stimulate the LACK-specific T cells. Amastigote-infected macrophages could, however, reactivate the T cells if LACK-delta(1), a recombinant form of LACK, was added as an exogenous protein in the culture medium. Similar results were obtained with all combinations tested involving macrophages from various origins, different activating cytokines (IFN-gamma, granulocyte-macrophage CSF, IL-4), several Leishmania species (L. amazonensis, L. major, L. donovani), and 15 different LACK-reactive T cell hybrids and clones. From these data, it is tempting to propose that the differentiation of promastigotes into amastigotes, which leads to a better survival of the parasites within macrophages, also allows them to go unnoticed by the immune system.
巨噬细胞显然是体内唯一能让细胞内病原体利什曼原虫生长的细胞。因此，它们通常被认为是向已知参与保护性和反保护性免疫反应的CD4+ T淋巴细胞呈递寄生虫抗原的可能候选者。在本研究中，我们检测了感染利什曼原虫的小鼠巨噬细胞是否能够刺激T细胞杂交瘤和一个与先前鉴定的保护性抗原LACK（活化C激酶受体的利什曼原虫同源物）发生反应的T细胞克隆。这种寄生虫蛋白在利什曼原虫的前鞭毛体和无鞭毛体阶段均有表达。我们发现，用γ干扰素处理过的、最近感染了活的利什曼原虫前鞭毛体的巨噬细胞完全有能力激活对LACK有反应的T细胞。然而，在感染后期，尽管存在大量细胞内寄生虫，但感染前鞭毛体的许可性巨噬细胞不再能够呈递LACK。LACK的这种即时呈递显然与细胞内寄生虫至少部分被破坏有关。相比之下，感染活的利什曼原虫无鞭毛体的巨噬细胞始终无法刺激对LACK特异的T细胞。然而，如果将重组形式的LACK即LACK-δ(1)作为外源性蛋白添加到培养基中，感染无鞭毛体的巨噬细胞可以重新激活T细胞。在涉及来自不同来源的巨噬细胞、不同的活化细胞因子（γ干扰素、粒细胞巨噬细胞集落刺激因子、白细胞介素-4）、几种利什曼原虫物种（亚马逊利什曼原虫、硕大利什曼原虫、杜氏利什曼原虫）以及15种不同的对LACK有反应的T细胞杂交瘤和克隆的所有测试组合中，均获得了类似结果。根据这些数据，很容易推测前鞭毛体向无鞭毛体的分化，这使得寄生虫在巨噬细胞内有更好的存活能力，也使它们能够不被免疫系统察觉。
