David H. Smith Center for Vaccine Biology and Immunology, Aab Institute of Biomedical Sciences, Rochester, NY, USA.
Immunol Res. 2009 Dec;45(2-3):209-17. doi: 10.1007/s12026-009-8102-0. Epub 2009 Feb 18.
CD8+ T cells are critically important for immune defense against many viral and bacterial pathogens, and are also key components of cancer immunotherapy. Help from CD4+ T cells is usually essential for optimal CD8+ T cell responses, driving the primary response, the survival of memory cells, and the generation of protective and therapeutic immunity. Understanding the mechanisms of help is thus essential for vaccine design, and for restoring protective immunity in immunosuppressed individuals. Our laboratory has developed an immunization protocol using peptide-pulsed dendritic cells to stimulate help-dependent primary, memory, and secondary CD8+ T cell responses. We have used gene-targeted and T cell receptor transgenic mice to identify two distinct pathways that generate help-dependent and help-independent CD8+ T cell responses, respectively, and are now starting to define the molecular mechanisms underlying these two pathways.
CD8+ T 细胞对于抵抗许多病毒和细菌病原体的免疫防御至关重要,也是癌症免疫疗法的关键组成部分。CD4+ T 细胞的帮助通常对于最佳 CD8+ T 细胞反应至关重要,它可以驱动初始反应、记忆细胞的存活以及保护性和治疗性免疫的产生。因此,了解辅助的机制对于疫苗设计以及恢复免疫抑制个体的保护性免疫至关重要。我们的实验室开发了一种使用肽脉冲树突状细胞刺激辅助依赖性原发性、记忆性和继发性 CD8+ T 细胞反应的免疫方案。我们已经使用基因靶向和 T 细胞受体转基因小鼠来分别鉴定出产生辅助依赖性和辅助非依赖性 CD8+ T 细胞反应的两条不同途径,现在我们开始定义这两条途径的分子机制。