Galli Grazia, Pittoni Paola, Tonti Elena, Malzone Carmine, Uematsu Yasushi, Tortoli Marco, Maione Domenico, Volpini Gianfranco, Finco Oretta, Nuti Sandra, Tavarini Simona, Dellabona Paolo, Rappuoli Rino, Casorati Giulia, Abrignani Sergio
Novartis Vaccines, Via Fiorentina 1, 53100 Siena, Italy.
Proc Natl Acad Sci U S A. 2007 Mar 6;104(10):3984-9. doi: 10.1073/pnas.0700191104. Epub 2007 Feb 27.
Invariant natural killer T (iNKT) cells are innate-like lymphocytes recognizing CD1d-restricted glycolipid antigens, such as alpha-galactosylceramide (alphaGC). We assessed whether iNKT cells help B lymphocyte responses and found that mice immunized with proteins and alphaGC develop antibody titers 1-2 logs higher than those induced by proteins alone. Activation of iNKT cells enhances protection against infections such as influenza and elicits higher frequencies of memory B cells and higher antibody responses to booster immunizations. Protein vaccination with alphaGC, but not with conventional adjuvants, elicits IgG responses in mice lacking MHC class II molecules, demonstrating that iNKT cells can substitute for CD4(+) T cell help to B cells. Interestingly, the decay of circulating antibodies is faster in mice lacking iNKT cells. These findings point to a homeostatic role for iNKT cells on critical features of the antibody response such as immunity and B cell memory.
不变自然杀伤T（iNKT）细胞是一类固有样淋巴细胞，可识别CD1d限制性糖脂抗原，如α-半乳糖神经酰胺（αGC）。我们评估了iNKT细胞是否有助于B淋巴细胞反应，发现用蛋白质和αGC免疫的小鼠产生的抗体滴度比仅用蛋白质诱导的抗体滴度高1至2个对数。iNKT细胞的激活增强了对流感等感染的抵抗力，并引发了更高频率的记忆B细胞以及对加强免疫的更高抗体反应。用αGC而非传统佐剂进行蛋白质疫苗接种，可在缺乏MHC II类分子的小鼠中引发IgG反应，这表明iNKT细胞可替代CD4(+) T细胞对B细胞的辅助作用。有趣的是，在缺乏iNKT细胞的小鼠中，循环抗体的衰减更快。这些发现表明iNKT细胞在抗体反应的关键特征（如免疫和B细胞记忆）中具有稳态作用。
