LEISHMANIA-DONOVANI-REACTIVE TH1-LIKE AND TH2-LIKE T-CELL CLONES FROM INDIVIDUALS WHO HAVE RECOVERED FROM VISCERAL LEISHMANIASIS
LEISHMANIA-DONOVANI-REACTIVE TH1-LIKE AND TH2-LIKE T-CELL CLONES FROM INDIVIDUALS WHO HAVE RECOVERED FROM VISCERAL LEISHMANIASIS
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DOI：
10.1128/iai.61.3.1069-1073.1993
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发表时间：
1993-03-01
影响因子：
3.1
通讯作者：
THEANDER, TG
中科院分区：
文献类型：
--
作者：
KEMP, M;KURTZHALS, JAL;THEANDER, TG
杜氏利什曼原虫在人类中的感染可导致致命性疾病内脏利什曼病（VL）或自限性无症状感染。在使用硕大利什曼原虫的感染的鼠模型中，疾病的过程可以通过产生白细胞介素-4（IL-4）的Th 2细胞被导向VL样综合征，或者通过分泌γ干扰素（IFN-γ）的Th 1细胞治愈。本研究检测了人T细胞对L. donovani。在一组L. Donovani反应性CD 4+人T细胞克隆产生自锑治疗后从VL恢复的个体。两个T细胞克隆产生大量IL-4而不产生IFN-γ，七个克隆产生IFN-γ和IL-4，八个克隆仅产生IFN-γ。这是第一次报告的Th 1和Th 2型反应在人类利什曼病。这些结果表明，与小鼠模型类似，人类T细胞对L。Donovani感染产生IL-4的Th 2样细胞的优先活化可能参与人VL的恶化，而产生IFN-γ的Th 1细胞的活化可能保护宿主免于严重疾病。识别激活一种或另一种类型的T细胞的利什曼抗原将在针对利什曼病的疫苗的开发中是重要的。
Infections in humans by Leishmania donovani parasites can result in a fatal disease, visceral leishmaniasis (VL), or in a self-limiting asymptomatic infection. In murine models of the infection employing Leishmania major, the course of the disease can be directed into a VL-like syndrome by interleukin-4 (IL-4)-producing Th2 cells, or cure may result by Th1 cells secreting gamma interferon (IFN-gamma). The present study examined the potential of human T cells to generate Th1 or Th2 responses to L. donovani. The profiles of IFN-gamma, IL-4, and lymphotoxin secretion after antigen stimulation were analyzed in a panel of L. donovani-reactive CD4+ human T-cell clones generated from individuals who had recovered from VL after antimonial treatment. Two of the T-cell clones produced large amounts of IL-4 without production of IFN-gamma, seven clones produced both IFN-gamma and IL-4, and eight produced only IFN-gamma. This is the first report of a Th1- and Th2-type response in human leishmaniasis. These results suggest that in analogy with murine models, there is a dichotomy in the human T-cell response to L. donovani infections. Preferential activation of IL-4-producing Th2-like cells may be involved in the exacerbation of human VL, whereas activation of IFN-gamma-producing Th1 cells may protect the host from severe disease. Identification of leishmanial antigens activating one or the other type of T cells will be important in the development of vaccines against leishmaniasis.