Oxidized low-density lipoprotein modulates differentiation of murine memory CD8+ T cell subpopulations

ZHENG Hua; LIN Zehang; ZHANG Yanmei; ZHOU Chenfei; LIU Xuan; WU Sha

doi:10.3969/j.issn.1673-4254.2017.08.16

Abstract：Objective To investigate effect of oxidized low-density lipoprotein (ox-LDL) on memory CD8+T cell subpopulation differentiation in mice with autoimmune diabetes. Methods Cultured splenic CD8 + T cells from pre-diabetic NOD mice isolated with magnetic beads were treated with 30 μg/mL ox-LDL and 10 U/mL interleukin-2 (IL-2) for 24 h and the control cells were treated with IL-2 only. Flow cytometry was used to determine the percentage of splenic CD8 +IFN-γ + T cells, expressions of CD8, CD44 and CD62L on the T cells, and the activation of T cell factor-1 (TCF-1) and STAT-3. The CD127+memory T cells were purified and transplanted into the pre-diabetic NOD mice via the tail vein, and the blood glucose was recorded weekly and survival time of the mice was monitored. Results Treatment with ox-LDL significantly reduced islet βcell-specific cytotoxic CD8+T cells as compared with the control group[(0.7±0.03)%vs (2.7±0.14)%, P<0.01]. The percentage of effector memory CD8+T cells (Tem) in the total memory CD8+T cells was reduced[(10.3 ± 0.71)%vs (30.3 ± 1.36)%, P<0.01]and that of stem cell-like memory T cells was significantly increased [(72.3 ± 3.8)% vs (55.1 ± 2.61)%, P<0.05] following ox-LDL treatment, which also resulted in significantly decreased activation of TCF-1 [(14.5 ± 0.82)% vs (34.2 ± 1.23)%, P<0.01] and pSTAT-3[(3.3 ± 0.12)% vs (22.1 ± 1.1)%, P<0.01]. Transplantation of ox-LDL-treated memory T cells in pre-diabetic NOD mice obviously inhibited the increase of blood glucose and prolonged the survival time of the mice (P<0.05). Conclusion Ox-LDL decreases the activation of transcriptional factors TCF-1 and phosphorylation of STAT-3, inhibits the formation of effector memory CD8 + T cells with long-term cytotoxicity, but promote the generation of stem cell-like memory CD8+ T cells, which result in suppression of islet β cell-specific effector cytotoxic CD8 + T cell differentiation to lessen autoimmune injury to the isletβcells.