Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond, Va.
Division of Rheumatology, Allergy and Immunology, Virginia Commonwealth University, Richmond, Va.
J Allergy Clin Immunol. 2018 Jan;141(1):311-321.e10. doi: 10.1016/j.jaci.2017.02.048. Epub 2017 Jun 15.
Mast cells (MCs), the primary effector cell of the atopic response, participate in immune defense at host/environment interfaces, yet the mechanisms by which they interact with CD4 T cells has been controversial.
We used in situ-matured primary human MCs and matched CD4 T cells to diligently assess the ability of MCs to act as antigen-presenting cells.
We examined mature human skin-derived MCs using flow cytometry for expression of antigen-presenting molecules, for their ability to stimulate CD4 T cells to express CD25 and proliferate when exposed to superantigen or to cytomegalovirus (CMV) antigen using matched T cells and MCs from CMV-seropositive or CMV-seronegative donors, and for antigen uptake. Subcellular localization of antigen, HLA molecules, and tryptase was analyzed by using structured illumination microscopy.
Our data show that IFN-γ induces HLA class II, HLA-DM, CD80, and CD40 expression on MCs, whereas MCs take up soluble and particulate antigens in an IFN-γ-independent manner. IFN-γ-primed MCs guide activation of T cells by Staphylococcus aureus superantigen and, when preincubated with CMV antigens, induce a recall CD4 T1 proliferation response only in CMV-seropositive donors. MCs co-opt their secretory granules for antigen processing and presentation. Consequently, MC degranulation increases surface delivery of HLA class II/peptide, further enhancing stimulation of T-cell proliferation.
IFN-γ primes human MCs to activate T cells through superantigen and to present CMV antigen to T1 cells, co-opting MC secretory granules for antigen processing and presentation and creating a feed-forward loop of T-cell-MC cross-activation.
肥大细胞（MCs）是过敏反应的主要效应细胞，参与宿主/环境界面的免疫防御，但它们与 CD4 T 细胞相互作用的机制一直存在争议。
我们使用原位成熟的原代人 MCs 和匹配的 CD4 T 细胞，努力评估 MCs 作为抗原呈递细胞的能力。
我们使用流式细胞术检查成熟的人皮肤来源的 MCs，以检查其表达抗原呈递分子的能力，以及在暴露于超抗原或巨细胞病毒（CMV）抗原时，用匹配的 T 细胞和来自 CMV 血清阳性或 CMV 血清阴性供体的 MCs 刺激 CD4 T 细胞表达 CD25 和增殖的能力，以及抗原摄取能力。使用结构照明显微镜分析抗原、HLA 分子和类胰蛋白酶的亚细胞定位。
我们的数据表明，IFN-γ诱导 MCs 表达 HLA Ⅱ类、HLA-DM、CD80 和 CD40，而 MCs 以 IFN-γ 不依赖的方式摄取可溶性和颗粒性抗原。IFN-γ 预处理的 MCs 通过金黄色葡萄球菌超抗原引导 T 细胞的活化，并且当与 CMV 抗原预孵育时，仅在 CMV 血清阳性供体中诱导回忆性 CD4 T1 增殖反应。MCs 采用其分泌颗粒进行抗原加工和呈递。因此，MC 脱颗粒增加了 HLA Ⅱ类/肽的表面递呈，进一步增强了对 T 细胞增殖的刺激。
IFN-γ 通过超抗原对人 MCs 进行致敏以激活 T 细胞，并将 CMV 抗原呈递给 T1 细胞，采用 MC 分泌颗粒进行抗原加工和呈递，并创建 T 细胞-MC 交叉激活的正反馈循环。
