Li Junxin, Sun Wenji, Subrahmanyam Priyanka B, Page Carly, Younger Kenisha M, Tiper Irina V, Frieman Matthew, Kimball Amy S, Webb Tonya J
Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Department of Medicine and the Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Med Sci (Basel). 2014 Jun 1;2(2):82-97. doi: 10.3390/medsci2020082.
Natural killer T (NKT) cells are a unique subset of CD1d-restricted T lymphocytes that express characteristics of both T cells and natural killer cells. NKT cells mediate tumor immune-surveillance; however, NKT cells are numerically reduced and functionally impaired in lymphoma patients. Many hematologic malignancies express CD1d molecules and co-stimulatory proteins needed to induce anti-tumor immunity by NKT cells, yet most tumors are poorly immunogenic. In this study, we sought to investigate NKT cell responses to B cell lymphoma. In the presence of exogenous antigen, both mouse and human NKT cell lines produce cytokines following stimulation by B cell lymphoma lines. NKT cell populations were examined in mouse models of spontaneous B cell lymphoma, and it was found that during early stages, NKT cell responses were enhanced in lymphoma-bearing animals compared to disease-free animals. In contrast, in lymphoma-bearing animals with splenomegaly and lymphadenopathy, NKT cells were functionally impaired. In a mouse model of blastoid variant mantle cell lymphoma, treatment of tumor-bearing mice with a potent NKT cell agonist, α-galactosylceramide (α-GalCer), resulted in a significant decrease in disease pathology. studies demonstrated that NKT cells from α-GalCer treated mice produced IFN-γ following α-GalCer restimulation, unlike NKT cells from vehicle-control treated mice. These data demonstrate an important role for NKT cells in the immune response to an aggressive hematologic malignancy like mantle cell lymphoma.
自然杀伤T（NKT）细胞是CD1d限制性T淋巴细胞的一个独特亚群，兼具T细胞和自然杀伤细胞的特性。NKT细胞介导肿瘤免疫监视；然而，淋巴瘤患者体内的NKT细胞数量减少且功能受损。许多血液系统恶性肿瘤表达NKT细胞诱导抗肿瘤免疫所需的CD1d分子和共刺激蛋白，但大多数肿瘤的免疫原性较差。在本研究中，我们试图研究NKT细胞对B细胞淋巴瘤的反应。在外源抗原存在的情况下，小鼠和人类NKT细胞系在受到B细胞淋巴瘤系刺激后会产生细胞因子。在自发性B细胞淋巴瘤的小鼠模型中检测了NKT细胞群体，发现与无病动物相比，荷瘤动物在早期阶段NKT细胞反应增强。相反，在出现脾肿大和淋巴结病的荷瘤动物中，NKT细胞功能受损。在母细胞样变异型套细胞淋巴瘤的小鼠模型中，用强效NKT细胞激动剂α-半乳糖神经酰胺（α-GalCer）治疗荷瘤小鼠，可使疾病病理显著减轻。研究表明，与接受载体对照治疗小鼠的NKT细胞不同，来自α-GalCer治疗小鼠的NKT细胞在α-GalCer再次刺激后会产生γ干扰素。这些数据证明了NKT细胞在针对侵袭性血液系统恶性肿瘤如套细胞淋巴瘤的免疫反应中发挥重要作用。
