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Báo cáo sinh học: " Spectratyping analysis of the islet-reactive T cell repertoire in diabetic NOD Igμnull mice after polyclonal B cell reconstitution"

Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành hóa học dành cho các bạn yêu hóa học tham khảo đề tài: Spectratyping analysis of the islet-reactive T cell repertoire in diabetic NOD Igμnull mice after polyclonal B cell reconstitution | Vong et al. Journal of Translational Medicine 2011 9 101 http www.translational-medicine.eom content 9 1 101 JOURNAL OF TRANSLATIONAL MEDICINE RESEARCH Open Access Spectratyping analysis of the islet-reactive T cell repertoire in diabetic NOD Igp mice after polyclonal B cell reconstitution Allen M Vong Nazila Daneshjou Patricia Y Norori Huiming Sheng Todd A Braciak Eli E Sercarz and Claudia Raja Gabaglia Abstract Background Non Obese Diabetic mice lacking B cells NOD.Ig dnullmice do not develop diabetes despite their susceptible background. Upon reconstitution of B cells using a chimera approach animals start developing diabetes at 20 weeks of age. Methods We have used the spectratyping technique to follow the T cell receptor TCR V beta repertoire of NOD. Iggnullmice following B cell reconstitution. This technique provides an unbiased approach to understand the kinetics of TCR expansion. We have also analyzed the TCR repertoire of reconstituted animals receiving cyclophosphamide treatment and following tissue transplants to identify common aggressive clonotypes. Results We found that B cell reconstitution of NOD.Ig dnullmice induces a polyclonal TCR repertoire in the pancreas 10 weeks later gradually diversifying to encompass most BV families. Interestingly these clonotypic BV expansions are mainly confined to the pancreas and are absent from pancreatic lymph nodes or spleens. Cyclophosphamide-induced diabetes at 10 weeks post-B cell reconstitution reorganized the predominant TCR repertoires by removing potential regulatory clonotypes BV1 BV8 and BV11 and increasing the frequency of others BV4 BV5S2 BV9 BV16-20 . These same clonotypes are more frequently present in neonatal pancreatic transplants under the kidney capsule of B-cell reconstituted diabetic NOD.Ig dnullmice suggesting their higher invasiveness. Phenotypic analysis of the pancreas-infiltrating lymphocytes during diabetes onset in B cell reconstituted animals show a predominance of CD19 B cells with a B