Kreuzer D, Nikoopour E, Au B C Y, Krougly O, Lee-Chan E, Summers K L, Haeryfar S M M, Singh B
Centre for Human Immunology, Department of Microbiology and Immunology and Robarts Research Institute, University of Western Ontario, London, ON, Canada.
Clin Exp Immunol. 2015 Feb;179(2):245-55. doi: 10.1111/cei.12462.
The increased risk and persistence of infections in diabetic condition is probably associated with defects in the cellular immune responses. We have previously shown a decrease in the production of interferon (IFN)-α by dendritic cells (DCs) in diabetic subjects. The basal level of IFN-α in splenic plasmacytoid DCs (pDCs) is also lower in non-obese diabetic (NOD) mice compared to prediabetic mice. The objective of this study was to analyse the ability of diabetic mice to mobilize innate and CD8(+) T cell-mediated immune response to influenza A virus (IAV) with the live influenza A/Puerto Rico/8/1934 H1N1 (PR8) strain or with its immunodominant CD8(+) T cell epitopes. We found that following immunization with IAV, the level of IFN-α in diabetic mice was increased to the level in prediabetic mice. Immunization of NOD mice with the immunodominant IAV PR8 peptide induced clonal expansion of IFN-γ-producing CD8(+) T cells similar to the response observed in prediabetic mice. Thus, diabetic and prediabetic NOD mice have a similar capacity for IFN-α and IFN-γ production by pDCs and CD8(+) T cells, respectively. Therefore, the DC-related immune defect in diabetic NOD mice does not impair their capacity to develop an effective immune response to IAV. Our results suggest that reduced IFN-α production by diabetic human and mouse DCs is not an impediment to an effective immunity to IAV in type 1 diabetic subjects vaccinated with live attenuated influenza vaccine.
糖尿病状态下感染风险增加及持续存在可能与细胞免疫反应缺陷有关。我们之前已表明，糖尿病患者树突状细胞（DC）产生干扰素（IFN）-α的能力下降。与糖尿病前期小鼠相比，非肥胖糖尿病（NOD）小鼠脾浆细胞样DC（pDC）中IFN-α的基础水平也较低。本研究的目的是分析糖尿病小鼠动员先天性免疫和CD8(+) T细胞介导的针对甲型流感病毒（IAV）活甲型/波多黎各/8/1934 H1N1（PR8）株或其免疫显性CD8(+) T细胞表位的免疫反应的能力。我们发现，用IAV免疫后，糖尿病小鼠体内IFN-α水平升高至糖尿病前期小鼠的水平。用免疫显性IAV PR8肽免疫NOD小鼠可诱导产生IFN-γ的CD8(+) T细胞克隆性扩增，类似于在糖尿病前期小鼠中观察到的反应。因此，糖尿病和糖尿病前期NOD小鼠分别在pDC和CD8(+) T细胞产生IFN-α和IFN-γ方面具有相似的能力。所以，糖尿病NOD小鼠中与DC相关的免疫缺陷并不损害它们对IAV产生有效免疫反应的能力。我们的结果表明，糖尿病患者和小鼠DC产生IFN-α减少，对于接种减毒活流感疫苗的1型糖尿病患者对IAV产生有效免疫而言并非障碍。
