IN VIVO PRIMING OF T HELPER CELLS WITH IL12 OR IL4

用 IL12 或 IL4 体内启动辅助细胞

• 批准号: 2057527
• 负责人: BARBARA R VON BEUST
• 金额: $ 4.7万
• 依托单位: WASHINGTON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-09-30 至 1997-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2057527
• 关键词: cow; cytokine; gene expression; helper T lymphocyte; interferon gamma; interleukin 4; leukemia virus; leukocyte activation /transformation; tissue /cell culture; transfection; transfection /expression vector; vaccinia virus; virus antigen; cow; cytokine; gene expression; helper T lymphocyte; interferon gamma; interleukin 4; leukemia virus; leukocyte activation /transformation; tissue /cell culture; transfection; transfection /expression vector; vaccinia virus; virus antigen

The expression of different T helper (TH) lymphocyte phenotypes is primed upon antigen presentation and is reciprocally mediated by the initiation cytokines IL-12 for TH1 expression and IL-4 for TH2 expression. TH phenotype expression has recently been associated with the outcome of human immunodeficiency virus (HIV) infection. Some individuals belonging to high risk groups repeatedly exposed to HIV remain antigen and antibody negative while exhibiting strong TH1 responses to a HIV env peptide representing a T-cell epitope. Furthermore, the development of immunodeficiency correlates with the progressive loss of TH1 phenotype expression, while TH2 phenotype expression becomes more dominant. However, the role of the TH1 phenotype in immune protection to natural retroviral disease in humans and other outbred species has not been directly tested experimentally. It is proposed to initiate the TH1 or TH2 phenotype in response to a defined antigen [Bovine Leukemia Virus (BLV) env gp51] in outbred cattle in vivo by coexpression with recombinant bovine (rb) IL-12 or rbIL-4 in a vaccinia vector. This strategy will allow testing of the role of defined TH phenotypes in immune protection to BLV, an exogenous, lymphotropic leukemia virus closely related to HTLV-I and II. The hypothesis that inoculation of cattle with a vaccinia vector coexpressing rbIL-12 and the BLVenv gene will enhance TH1 expression, whereas inoculation with a vaccinia vector coexpressing rbIL-4 and the BLVenv gene will enhance TH2 expression will be tested by 3 specific aims: 1] Express functional recombinant bovine IL-12. 2] Construct vaccinia recombinants expressing the BLVenv gene in combination with rbIL-2 or rbIL-4. 3] Document the cytokine profile expressed by BLV env specific CD4+ lymphocytes primed in cattle inoculated with the recombinant vaccinia vectors defined in aim #2.

不同T辅助器（Th）淋巴细胞表型的表达是 以抗原表现为启动，并由 启动细胞因子IL-12用于Th1表达，Th2的IL-4 表达。 表型表达最近与 人免疫缺陷病毒（HIV）感染的结果。 一些 属于高风险群体的个人反复接触艾滋病毒 在表现强Th1的同时保持抗原和抗体阴性 对代表T细胞表位的HIV ENV肽的反应。 此外，免疫缺陷的发展与 Th1表型表达的进行性丧失，而Th2表型 表达变得更加主导。 但是，TH1的作用 免疫保护自然逆转录病毒疾病的表型 和其他杂种物种尚未直接通过实验进行测试。 提议响应A启动Th1或Th2表型 定义的抗原[牛白血病病毒（BLV）ENV GP51] 通过与重组牛（RB）IL-12或Rbil-4共表达体内 离子载体。 该策略将允许测试 在免疫保护中定义了表型，是外源性的BLV 与HTLV-I和II密切相关的淋巴细胞性白血病病毒。 这 假设用离甲酸载体接种牛 共表达RBIL-12和BLVENV基因将增强Th1表达， 而接种vocinia vector的接种rbil-4和 Blvenv基因将增强Th2表达，将通过3个特定 目的：1]表达功能重组牛IL-12。 2]构造 表达Blvenv基因的疫苗重组者与 RBIL-2或RBIL-4。 3]记录BLV Env表示的细胞因子谱 特定的CD4+淋巴细胞在接种的牛中引发 AIM＃2中定义的重组疫苗向量。