Wang Yufei, Rahman Durdana, Mistry Mukesh, Lehner Thomas
From the Mucosal Immunology Unit, King's College London at Guy's Hospital, London SE1 1UT, United Kingdom.
From the Mucosal Immunology Unit, King's College London at Guy's Hospital, London SE1 1UT, United Kingdom
J Biol Chem. 2016 Sep 23;291(39):20707-17. doi: 10.1074/jbc.M116.746057. Epub 2016 Aug 8.
Immunological memory is a fundamental function of vaccination. The antigenic breakdown products of the vaccine may not persist, and undefined tonic stimulation has been proposed to maintain the specific memory. We have suggested that cellular stress agents to which the immune cells are constantly exposed may be responsible for tonic stimulation. Here we have studied four stress agents: sodium arsenite, an oxidative agent; Gramicidin, eliciting K(+) efflux and calcium influx; dithiocarbamate, a metal ionophore; and aluminum hydroxide (alum), an immunological adjuvant. The aims of this study are to extend these investigations to T and B cell responses of unimmunized and ovalbumin (OVA)-immunized BALB/c mice, and furthermore, to ascertain whether stress is involved in optimal expression of memory B cells, as demonstrated in CD4(+) T cells. Examination of the homeostatic pathway defined by IL-15/IL-15R (IL-15 receptor) interaction and the inflammasome pathway defined by the IL-1-IL-1R interaction between dendritic cells (DC) and CD4(+) T cells suggests that both pathways are involved in the development of optimal expression of CD4(+)CD45RO(+) memory T cells in unimmunized and OVA-immunized BALB/c mice. Furthermore, significant direct correlation was found between CD4(+)CD44(+) memory T cells and both IL-15 of the homeostatic and IL-1β of the inflammasome pathways. However, CD19(+)CD27(+) memory B cells in vivo seem to utilize only the IL-15/IL-15R homeostatic pathway, although the proliferative responses are enhanced by the stress agents. Altogether, stress agents may up-regulate unimmunized and OVA-immunized CD4(+)CD44(+) memory T cells by the homeostatic and inflammasome pathways. However, the CD19(+)CD27(+) memory B cells utilize only the homeostatic pathway.
免疫记忆是疫苗接种的一项基本功能。疫苗的抗原分解产物可能不会持续存在，有人提出未明确的持续刺激来维持特异性记忆。我们曾提出，免疫细胞持续接触的细胞应激剂可能是持续刺激的原因。在此，我们研究了四种应激剂：亚砷酸钠，一种氧化剂；短杆菌肽，可引发钾离子外流和钙离子内流；二硫代氨基甲酸盐，一种金属离子载体；以及氢氧化铝（明矾），一种免疫佐剂。本研究的目的是将这些研究扩展至未免疫和经卵清蛋白（OVA）免疫的BALB/c小鼠的T细胞和B细胞反应，此外，确定应激是否如在CD4(+) T细胞中所证实的那样，参与记忆B细胞的最佳表达。对由白细胞介素-15/白细胞介素-15受体（IL-15R）相互作用所定义的稳态途径以及由树突状细胞（DC）与CD4(+) T细胞之间的白细胞介素-1-白细胞介素-1受体相互作用所定义的炎性小体途径的研究表明，这两条途径均参与未免疫和经OVA免疫的BALB/c小鼠中CD4(+)CD45RO(+)记忆T细胞最佳表达的形成。此外，在稳态途径的白细胞介素-15和炎性小体途径的白细胞介素-1β与CD4(+)CD44(+)记忆T细胞之间发现了显著的直接相关性。然而，体内的CD19(+)CD27(+)记忆B细胞似乎仅利用白细胞介素-15/白细胞介素-15R稳态途径，尽管应激剂可增强其增殖反应。总之，应激剂可能通过稳态途径和炎性小体途径上调未免疫和经OVA免疫的CD4(+)CD44(+)记忆T细胞。然而，CD19(+)CD27(+)记忆B细胞仅利用稳态途径。
