IMMUNOREGULATION IN MURINE MALARIA

在研究感染疟疾的小鼠时，我们首次表明 表达携带特定V-βT细胞受体元件的T细胞可以 影响传染病进程的结果。近交系 小鼠在抵抗致命病毒感染的能力上可能存在显著差异 或者疟疾寄生虫约氏疟原虫的非致命性分离株。我们有 显示MHC基因和定位在MHC外的基因，以及 寄生虫遗传因素影响这些感染的结果。我们的 现在的研究表明，在宿主中表达的内源性 小鼠乳腺肿瘤病毒(MTV-7)，最初被描述为 Mis-1a基因可以改变寄主抵抗约氏疟原虫的能力 感染。因为内源性小鼠乳腺肿瘤病毒，如MTV-7 编码与之反应的超抗原，然后实现缺失(或 无能)的T细胞携带特定的V-βTCR元件，我们进行 研究证实，已经明确耗尽T细胞的小鼠 携带相关V-βTCR元件的细胞在以下情况下具有抗感染能力 与拥有这种细胞的小鼠相比。我们的数据表明，它可能 无法预测疫苗接种试验的成功与否，或者 在事先不知道宿主的情况下疟疾感染的结果 暴露于由一系列其他感染性或 内源性因素。为了描述宿主的免疫反应， 在感染疟疾的小鼠中，受相关TCR携带细胞的调控，我们 将研究MTV-7(Mis-1)的体液和细胞免疫反应 同源小鼠品系和表达人人类白细胞抗原DQ的小鼠品系 已知的介导特定V-βTCR-T缺失的转基因 细胞。特异性耗尽某些V-βTCR-的小鼠的反应 通过注射V-β特异性单抗来承载细胞 或者Mis不同的细胞也将被描述。我们的数据表明 任何改变T细胞谱系的因素，无论是在之前还是之后 出生，可能会改变宿主抵抗疟疾的能力或 其他传染病。

Studying malaria-infected mice, we have shown for the first time that expression of T cells bearing specific V-beta T cell receptor elements can influence the outcome of an infectious disease process. Inbred strains of mice can differ markedly in their ability to resist infection with lethal or nonlethal isolates of the malaria parasite Plasmodium yoelii. We have shown that MHC genes and genes mapping outside the MHC, as well as parasite genetic factors influence the outcome of these infections. Our studies have now demonstrated that expression in the host of an endogenous mouse mammary tumor virus (MTV-7), originally described as the product of the Mis-1a gene, can alter the host's ability to resist P. yoelii infection. Because endogenous mouse mammary tumor viruses such as MTV-7 encode superantigens that react with and then effect the deletion (or anergy) of T cells bearing specific V-beta TCR elements, we conducted studies to confirm that mice that have been specifically depleted of T cells bearing relevant V-beta TCR elements are resistant to infection when compared to mice possessing such cells. Our data demonstrate that it may not be possible to predict the success of vaccination trials, or the outcome of malaria infections without prior knowledge of the host's exposure to superantigens expressed by an array of other infectious or endogenous agents. To characterize the host immune responses that are regulated by the relevant TCR-bearing cells in malaria-infected mice, we will study the humoral and cellular immune responses of MTV-7(Mis-1) congenic mouse strains, and mouse strains which express human HLA DQ transgenes known to mediate deletion of specific V-beta TCR-bearing T cells. Responses of mice specifically depleted of certain V-beta TCR- bearing cells by injection of either V-beta-specific monoclonal antibodies or Mis disparate cells will also be characterized. Our data suggest that any factor that alters the T cell repertoire, either before or after birth, could potentially alter the host's ability to resist malaria or other infectious diseases.