A Bispecific Protein Capable of Engaging CTLA-4 and MHCII Protects Non-Obese Diabetic Mice from Autoimmune DiabetesReportar como inadecuado




A Bispecific Protein Capable of Engaging CTLA-4 and MHCII Protects Non-Obese Diabetic Mice from Autoimmune Diabetes - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Crosslinking ligand-engaged cytotoxic T lymphocyte antigen-4 CTLA-4 to the T cell receptor TCR with a bispecific fusion protein BsB comprised of a mutant mouse CD80 and lymphocyte activation antigen-3 LAG-3 has been shown to attenuate TCR signaling and to direct T-cell differentiation toward Foxp3+ regulatory T cells Tregs in an allogenic mixed lymphocyte reaction MLR. Here, we show that antigen-specific Tregs can also be induced in an antigen-specific setting in vitro. Treatment of non-obese diabetic NOD female mice between 9–12 weeks of age with a short course of BsB elicited a transient increase of Tregs in the blood and moderately delayed the onset of autoimmune type 1 diabetes T1D. However, a longer course of treatment 10 weeks of 4–13 weeks-old female NOD animals with BsB significantly delayed the onset of disease or protected animals from developing diabetes, with only 13% of treated animals developing diabetes by 35 weeks of age compared to 80% of the animals in the control group. Histopathological analysis of the pancreata of the BsB-treated mice that remained non-diabetic revealed the preservation of insulin-producing β-cells despite the presence of different degrees of insulitis. Thus, a bifunctional protein capable of engaging CTLA-4 and MHCII and indirectly co-ligating CTLA-4 to the TCR protected NOD mice from developing T1D.



Autor: Hongmei Zhao , Jozsef Karman , Ji-Lei Jiang, Jinhua Zhang, Nathan Gumlaw, John Lydon, Qun Zhou, Huawei Qiu, Canwen Jiang, Seng H.

Fuente: http://plos.srce.hr/



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