IMMUNOREGULATION IN MURINE MALARIA

通过研究感染疟疾的小鼠，我们首次发现， 携带特异性V-β T细胞受体元件的T细胞的表达可 影响传染病进程的结果近交系 小鼠在抵抗致命感染的能力上可以显著不同， 或非致命的疟原虫分离物。我们有 表明MHC基因和MHC以外的基因，以及 寄生虫遗传因素影响这些感染的结果。我们 研究已经证明，在宿主中表达内源性 小鼠乳腺肿瘤病毒（MTV-7），最初被描述为 Mis-1a基因可以改变宿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 编码超抗原，所述超抗原与所述缺失（或 无反应性）的T细胞携带特定的V-β TCR元件，我们进行了 研究证实，已经特异性耗尽T细胞的小鼠 携带相关V-β TCR元件的细胞对感染具有抗性， 与拥有这些细胞的小鼠相比。我们的数据表明， 不可能预测疫苗接种试验的成功，或者 疟疾感染的结果，而事先不知道宿主的 暴露于由一系列其他感染性或 内源性因子为了表征宿主免疫反应， 在疟疾感染的小鼠中， 将研究MTV-7（Mis-1）的体液和细胞免疫应答 同类小鼠品系和表达人HLA DQ的小鼠品系 已知介导特异性携带V-β TCR的T细胞缺失的转基因 细胞特异性耗尽某些V-β TCR的小鼠的反应- 通过注射V-β特异性单克隆抗体 或Mis的不同细胞也将被表征。我们的数据表明 任何改变T细胞库的因素，无论是之前还是之后， 出生，可能会改变宿主抵抗疟疾的能力， 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.