Department of Microbiology and Immunology, Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201; and.
Department of Epidemiology and Public Health, Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201.
Immunohorizons. 2021 Mar 31;5(3):147-156. doi: 10.4049/immunohorizons.2000066.
NKT cells are primed lymphocytes that rapidly secrete cytokines and can directly kill cancerous cells. Given the critical role NKT cells play in cancer immune surveillance, we sought to investigate the effect of mutations in Brca1, specifically a conditional deletion of exon 11, on type I invariant NKT cell development. We observed a significant reduction in invariant NKT cells in both primary lymphoid and peripheral organs in Brca1 mutant mice compared with wild-type C57BL/6. However, the original Brca1 mutant strain was on a mixed background containing FVB/N. We determined that strain differences, rather than mutations in Brca1, led to the observed loss in NKT cells. Importantly, we found that whereas FVB/N mice lack Vβ8, there was a striking increase in the total number of thymic type I CD1d-α-galactosylceramide tetramer positive NKT cells and skewing of the NKT cell population to NKT2 compared with C57BL/6 mice. Collectively, our data demonstrate the profound effect genetics can have on NKT cell subset differentiation.
NKT 细胞是经过预先致敏的淋巴细胞，能够迅速分泌细胞因子，并可以直接杀死癌细胞。鉴于 NKT 细胞在癌症免疫监测中发挥着关键作用，我们试图研究 Brca1 基因突变，特别是 11 号外显子的条件性缺失，对 I 型不变 NKT 细胞发育的影响。与野生型 C57BL/6 相比，我们观察到 Brca1 突变小鼠的初级淋巴器官和外周器官中的不变 NKT 细胞数量明显减少。然而，最初的 Brca1 突变株是在含有 FVB/N 的混合背景下。我们确定，是品系差异而不是 Brca1 突变导致了观察到的 NKT 细胞缺失。重要的是，我们发现虽然 FVB/N 小鼠缺乏 Vβ8，但与 C57BL/6 小鼠相比，胸腺 I 型 CD1d-α-半乳糖基神经酰胺四聚体阳性 NKT 细胞的总数显著增加，并且 NKT 细胞群向 NKT2 的偏向明显。总之，我们的数据表明遗传因素对 NKT 细胞亚群分化有深远的影响。
