Ehst Benjamin D, Ingulli Elizabeth, Jenkins Marc K
Department of Microbiology, Center for Immunology, University of Minnesota Medical School, Minneapolis, MN, USA.
Am J Transplant. 2003 Nov;3(11):1355-62. doi: 10.1046/j.1600-6135.2003.00246.x.
The goal of this study was the development of a system in which the cooperative interactions between CD4 and CD8 T cells specific for defined peptides from a single minor histocompatibility antigen could be studied. A transgenic mouse strain that expresses chicken ovalbumin (Act-mOVA) on the surface of all cells in the body was produced as a source of tissues containing such an antigen. Skin grafts from Act-mOVA donors were rapidly and completely rejected by wild-type recipients, but only when both CD4 and CD8 T cells were present. CD4 T cells by themselves caused an incomplete form of rejection characterized by rapid but partial contraction of Act-mOVA grafts. CD8 T cells alone caused complete rejection of Act-mOVA skin grafts but only after a long delay. Adoptively transferred ovalbumin-specific TCR-transgenic CD4 and CD8 T cells were stimulated by Act-mOVA graft antigens and CD8 T-cell accumulation in the grafts was enhanced by specific CD4 T cells. These findings, together with the fact that the ligand for ovalbumin peptide-specific CD8 T cells can be detected in Act-mOVA tissues with an MHC-restricted antibody, make this an ideal system for the study of cooperation between CD4 and CD8 T cells.
本研究的目标是开发一种系统，用于研究针对来自单一微小组织相容性抗原的特定肽段的CD4和CD8 T细胞之间的协同相互作用。构建了一种转基因小鼠品系（Act-mOVA），其体内所有细胞表面均表达鸡卵清蛋白，以此作为含有此类抗原的组织来源。来自Act-mOVA供体的皮肤移植被野生型受体迅速且完全排斥，但前提是CD4和CD8 T细胞均存在。单独的CD4 T细胞引起一种不完全的排斥形式，其特征为Act-mOVA移植物迅速但部分收缩。单独的CD8 T细胞可导致Act-mOVA皮肤移植物完全排斥，但会有较长延迟。Act-mOVA移植物抗原刺激过继转移的卵清蛋白特异性TCR转基因CD4和CD8 T细胞，并且特异性CD4 T细胞可增强移植物中CD8 T细胞的聚集。这些发现，连同使用MHC限制性抗体可在Act-mOVA组织中检测到卵清蛋白肽特异性CD8 T细胞的配体这一事实，使其成为研究CD4和CD8 T细胞之间协同作用的理想系统。
