Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, 9 Cambridge Center, Cambridge, MA 02142, USA.
Cell Rep. 2012 May 31;1(5):461-71. doi: 10.1016/j.celrep.2012.03.009. Epub 2012 Apr 26.
To study the CD8(+) T cell response against a mouse γ-herpes virus, we generated K(b)-MHV-68-ORF8(604-612)RAG(-/-) CD8(+) T cell receptor transnuclear (TN) mice as a source of virus-specific CD8(+) T cells. K(b)-ORF8-Tet(+) CD8(+) T cells, expanded in the course of a resolving MHV-68 infection, served as a source of nucleus donors. Various in vivo and ex vivo assay criteria demonstrated the fine specificity and functionality of TN cells. TN cells proliferated extensively in response to viral infection, helped control viral burden, and exhibited a phenotype similar to that of endogenous K(b)-ORF8-Tet(+) cells. When compared to OT-1 cells, TN cells displayed distinct properties in response to lymphopenia and cognate antigen stimulation, which may be attributable to the affinity of the TCR expressed by the TN cells. The availability of MHV-68-specific CD8(+) TCR TN mice provides a new tool for investigating aspects of host-pathogen interactions unique to γ-herpes viruses.
为了研究针对小鼠 γ-疱疹病毒的 CD8(+) T 细胞反应，我们生成了 K(b)-MHV-68-ORF8(604-612)RAG(-/-) CD8(+) T 细胞受体转核 (TN) 小鼠作为病毒特异性 CD8(+) T 细胞的来源。在解决 MHV-68 感染的过程中扩增的 K(b)-ORF8-Tet(+) CD8(+) T 细胞作为核供体的来源。各种体内和体外检测标准证明了 TN 细胞的精细特异性和功能。TN 细胞在病毒感染后广泛增殖，有助于控制病毒载量，并表现出与内源性 K(b)-ORF8-Tet(+)细胞相似的表型。与 OT-1 细胞相比，TN 细胞在应对淋巴细胞减少症和同源抗原刺激时表现出不同的特性，这可能归因于 TN 细胞表达的 TCR 的亲和力。MHV-68 特异性 CD8(+) TCR TN 小鼠的可用性为研究 γ-疱疹病毒特有的宿主-病原体相互作用提供了新的工具。
