Ghosh Amlan Kanti, Sinha Debolina, Mukherjee Subhadeep, Biswas Ratna, Biswas Tapas
Division of Immunology, National Institute of Cholera and Enteric Diseases, Kolkata, India.
Division of Immunology, National Institute of Cholera and Enteric Diseases, Kolkata, India.
Cytokine. 2015 May;73(1):44-52. doi: 10.1016/j.cyto.2015.01.018. Epub 2015 Feb 16.
Nonconventional innate memory CD8(+) T cells characteristically expressing CD44, CD122, eomesodermin (Eomes) and promyelocytic leukemia zinc finger (PLZF) were derived in culture from CD4(+)CD8(+) double positive (DP) thymocytes of normal BALB/c and C57BL/6 mice. These culture-differentiated cells constitutively express toll-like receptor (TLR)4 and release interferon (IFN)-γ and interleukin (IL)-10. We show the TLR4-ligand lipopolysaccharide (LPS) stimulate the TLR and up-regulate IFN-γ skewing the cells towards type 1 polarization. In presence of LPS these cells also express suppressor of cytokine signaling (SOCS)1 and thus suppress IL-10 expression. In contrast, heat shock protein (Hsp)70 down-regulated TLR4 augmenting the anti-inflammatory cytokine IL-10. In association with IL-10 release IFN-γ was abrogated. The programmed cell death (PD)-1 mostly present in regulatory T cells was stimulated in these IL-10 producing cells by Hsp70 and not LPS indicating the cells can be driven to two contrast outcomes by the two TLR4 ligands. Our work provides a scope for in vitro monitoring of CD8(+) T cells to decipher important immune therapeutic option during infection or sepsis.
非传统固有记忆性CD8(+) T细胞特征性地表达CD44、CD122、胚外中胚层决定蛋白（Eomes）和早幼粒细胞白血病锌指蛋白（PLZF），是从正常BALB/c和C57BL/6小鼠的CD4(+)CD8(+)双阳性（DP）胸腺细胞在培养物中衍生而来。这些培养分化的细胞组成性表达Toll样受体（TLR）4，并释放干扰素（IFN）-γ和白细胞介素（IL）-10。我们发现TLR4配体脂多糖（LPS）刺激TLR并上调IFN-γ，使细胞倾向于1型极化。在LPS存在的情况下，这些细胞还表达细胞因子信号转导抑制因子（SOCS）1，从而抑制IL-10的表达。相反，热休克蛋白（Hsp）70下调TLR4，增加抗炎细胞因子IL-10。与IL-10释放相关，IFN-γ被消除。程序性细胞死亡蛋白（PD）-1主要存在于调节性T细胞中，在这些产生IL-10的细胞中被Hsp70而非LPS刺激，这表明这两种TLR4配体可使细胞产生两种相反的结果。我们的工作为体外监测CD8(+) T细胞以解读感染或脓毒症期间重要的免疫治疗选择提供了空间。
