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 β cell-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 islet β cells.
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 β cell-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 islet β cells.
Authors: J Adam Best; David A Blair; Jamie Knell; Edward Yang; Viveka Mayya; Andrew Doedens; Michael L Dustin; Ananda W Goldrath Journal: Nat Immunol Date: 2013-02-10 Impact factor: 25.606