CD11a/ICAM-1 blockade combined with IL-2 targeting therapy causes a paradoxical acceleration of type 1 diabetes.

摘要: Enhancement of regulatory T-cell (Treg) function is the goal many immunotherapies aimed at treating type 1 diabetes (T1D). The use interleukin (IL)-2 hindered by its effects on other populations such as effector T cells and NK cells. Combination therapies suppressing while using IL-2 to expand Tregs could be beneficial have been trialed in T1D patients. We investigated a combination therapy αCD11a blocking antibody simultaneously suppress activation migration autoreactive When non-obese diabetic mice were treated with low-dose IL-2/anti-IL-2 complexes (IL-2c) αCD11a, significant Treg expansion occurred both spleen pancreas. Activation IFNγ production islet-specific was robustly suppressed periphery following IL-2c/αCD11a treatment. Surprisingly, accelerated onset compared control treatments. Analysis responsive found that increased CD8+ natural killer (NK) specifically within pancreas despite concomitant expansion. Blocking inhibitor FTY720 together IL-2c treatment also resulted intra-pancreatic cell populations. Thus, inhibiting into islets unleashes islet-resident pathogenic effectors presence low doses exogenous IL-2.