ANALYSIS OF T CELL RESPONSES IN HUMAN LEISHMANIASIS

人类利什曼病 T 细胞反应分析

• 批准号: 3803203
• 负责人: D SACKS
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3803203
• 关键词: Leishmania donovani; T lymphocyte; antigen presentation; antigen presenting cell; cellular immunity; helper T lymphocyte; human tissue; interferons; intracellular parasitism; leishmaniasis; leukocyte activation /transformation; microorganism immunology; monocyte; protozoal antigen; suppressor T lymphocyte

Immunity to infection by the intracellular parasitic Leishmania is mediated by sensitized T cells; however, the antigens which they recognize are still poorly defined. We have previously shown that the cell-mediated response of individuals with healed or healing forms of cutaneous leishmaniasis occurs to as many as 50-70 distinct antigens; however, it is unclear whether all the antigens capable of inducing a T cell response are important in protective immunity. As this question can only be addressed using purified distinct antigens directly in vaccine studies, and as these are most conveniently obtained through molecular cloning, we have begun to examine the T-cell immunogenicity of recombinant leishmanial antigens initially selected on the basis of their reactivity with human kala-azar serum. Although this approach relies upon overlap of T- and B-cell epitopes, a significant proportion of recombinants so selected showed immunogenicity in initial human T-cell proliferation assays. Work is presently underway to purify these putative T-cell antigens for further characterization. Investigation of the T cell response of leishmania patients to soluble antigen pulsed monocytes or monocytes infected with amastigotes has demonstrated the fundamental role of the CD4 subset of T cells in mounting both a proliferative and gamma interferon response to both sources of antigen. The role of CD8 cells in these responses varies between patients and the pattern of CD8 mediated response does not correlate with the source of antigen, i.e., endogenous (infected monocyte) or exogenous (antigen pulsed monocyte). Although no correlation was found between CD8 responses and live antigen, the use of live antigen to prestimulate patient cells has illustrated and enhanced gamma interferon response by mucocutaneous patient T cells when compared to cells from cutaneous patients.

介导对细胞内寄生利什曼原虫感染的免疫 通过致敏T细胞；然而，它们识别的抗原仍然是 定义不明确。 我们之前已经表明，细胞介导的反应 皮肤利什曼病已治愈或正在愈合的个体 发生于多达 50-70 种不同的抗原；然而，尚不清楚 是否所有能够诱导 T 细胞反应的抗原都是 对保护性免疫很重要。 由于这个问题只能解决 直接在疫苗研究中使用纯化的不同抗原，并且作为这些 最方便地通过分子克隆获得，我们已经开始 检查重组利什曼原虫抗原的 T 细胞免疫原性 最初选择的依据是它们与人类黑热病的反应性 血清。 尽管这种方法依赖于 T 细胞和 B 细胞的重叠 表位，如此选择的重组体的很大一部分显示 初始人类 T 细胞增殖测定中的免疫原性。 工作是 目前正在进行纯化这些假定的 T 细胞抗原以用于进一步 表征。 利什曼原虫 T 细胞反应的研究 患者接受可溶性抗原脉冲的单核细胞或单核细胞感染 无鞭毛体已证明 T 的 CD4 子集的基本作用 细胞同时产生增殖和γ干扰素反应 两种抗原来源。 CD8 细胞在这些反应中的作用各不相同 患者之间的差异以及 CD8 介导的反应模式并不 与抗原来源相关，即内源性（受感染的单核细胞） 或外源性（抗原脉冲单核细胞）。 虽然没有发现相关性 在 CD8 反应和活抗原之间，使用活抗原来 预刺激患者细胞已说明并增强了γ干扰素 与来自皮肤粘膜患者的细胞相比，患者 T 细胞的反应 皮肤病患者。