Xiao Zhengguo, Curtsinger Julie M, Prlic Martin, Jameson Stephen C, Mescher Matthew F
Center for Immunology and Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.
Int Immunol. 2007 Jun;19(6):733-43. doi: 10.1093/intimm/dxm039. Epub 2007 Jun 1.
CD8 T cell responses to vaccinia virus (VV) and a virus-encoded ovalbumin peptide (OVAP) epitope were examined using adoptively transferred OT-I T cells. The results demonstrate that upon intra-peritoneal challenge with ovalbumin-expressing VV (VV-OVAP), OT-I T cell proliferation occurs initially in lymph nodes and spleens followed by migration of the divided cells to the peritoneal cavity. Massive clonal expansion occurs in response to both the virus and the virus-encoded ovalbumin (OVA) epitope, as demonstrated using low numbers of adoptively transferred cells, and the responding OT-I cells display marked site-dependent functional heterogeneity with respect to IFN-gamma and tumor necrosis factor-alpha (TNF-alpha) production and granzyme B expression. OT-I cells responding to VV-OVAP develop the capacity to produce IFN-gamma in response to antigen as they proliferate and differentiate. In marked contrast, naive OT-I cells rapidly produce TNF-alpha upon antigen recognition, and this capacity declines as the cells proliferate in response to the virus, suggesting that this potent inflammatory cytokine may be important primarily during initiation of the response. At the peak of clonal expansion, a large fraction (30-60%) of the OT-I cells responding to the virus express high IL-7Ralpha levels, and the majority of these cells is subsequently lost. While high IL-7Ralpha expression may be necessary for a CD8 T cell to transition to memory, it is clearly not sufficient. Thus, OT-I cells responding to VV infection exhibit a high degree of heterogeneity within the responding population that differs depending on their anatomical location, despite the specificity and affinity of the TCR being identical on all of the cells.
使用过继转移的OT-I T细胞检测了CD8 T细胞对痘苗病毒（VV）和病毒编码的卵清蛋白肽（OVAP）表位的反应。结果表明，在用表达卵清蛋白的VV（VV-OVAP）进行腹腔攻击后，OT-I T细胞最初在淋巴结和脾脏中增殖，随后分裂的细胞迁移至腹腔。如使用少量过继转移细胞所证明的那样，针对病毒和病毒编码的卵清蛋白（OVA）表位均发生大量克隆扩增，并且应答的OT-I细胞在干扰素-γ和肿瘤坏死因子-α（TNF-α）产生以及颗粒酶B表达方面表现出明显的位点依赖性功能异质性。对VV-OVAP作出反应的OT-I细胞在增殖和分化时产生针对抗原的干扰素-γ的能力得到发展。与之形成鲜明对比的是，幼稚的OT-I细胞在识别抗原后迅速产生TNF-α，并且随着细胞对病毒的增殖，这种能力下降，这表明这种强效的炎性细胞因子可能主要在反应起始阶段起重要作用。在克隆扩增的高峰期，对病毒作出反应的大部分（30%-60%）OT-I细胞表达高水平的IL-7Rα，并且这些细胞中的大多数随后丢失。虽然高IL-7Rα表达对于CD8 T细胞转变为记忆细胞可能是必要的，但显然并不充分。因此，对VV感染作出反应的OT-I细胞在应答群体中表现出高度的异质性，尽管所有细胞上TCR的特异性和亲和力相同，但这种异质性因解剖位置而异。
