Interaction between Treg Apoptosis Pathways, Treg Function and HLA Risk Evolves during Type 1 Diabetes Pathogenesis
Figure 5
Fas/FasL T-cell apoptosis prevalent in RO T1D, LS T1D and Low HLA risk controls.
A) In vitro soluble FasL caused significantly lower T cell apoptosis (in both naïve-CD25 and Tregs) in healthy High HLA risk control subjects compared to RO T1D T cells (for both cell subset comparisons Mann-U-Whitney test was p = 0.016), suggesting that Fas/FasL is one of the prevalent apoptosis mechanism in RO T1D subjects, but not in High HLA risk control subjects. B) Treg apoptosis caused by soluble FasL (1/40 dilution – 600 ng/ml) in healthy control, RO T1D and LS T1D subjects was significantly reduced with pretreatment with caspase 3 inhibitor Z-DEVD in majority of subjects. However, analysis of RO T1D subjects alone (red symbols) showed their better responsiveness to pretreatment with Ac-IETD compared to Z-DEVD. C) Activation-induced Treg apoptosis by anti-CD3 was moderately prevented through treatment of both inhibitors, suggesting an involvement of both caspase 3 and 8 in this apoptosis pathway in all subject groups. RO T1D subjects were labeled with red symbols. Mann-U-Whitney test was used for comparisons.