A relatively common autoimmune disease, Type 1 Diabetes (T1D) is still not well understood. It is known that T1D is caused by immune destruction of insulin-producing β cells and although it is widely believed that autoreactive T cells recognizing β cell antigens (eg. insulin) play a critical role in the disease onset and progression, researchers still have little direct evidence of the disease’s specific mechanisms and immunopathology. To this day, patients with T1D continue to rely on external insulin sources to control the disease, and even the best managed insulin therapies do not eliminate a patient’s risk for life threatening complications.
One critical deficit in our understanding of Type 1 Diabetes is the lack of humanized in vivo models that effectively allow for the study of immunopathogenesis and immunotherapies. Until recently, when patient blood lymphocytes were introduced to immunodeficient mice, xenogeneic graft-versus-host reactivity was observed, which made it nearly impossible to accurately observe and assess autoimmune responses.
However, a recent paper by Tan, et al published in the Early Edition of Proceedings of the National Academy of Sciences of the United States of America suggests that a new humanized mouse T1D model “containing robust human immune repertoires lacking xenogeneic graft-versus-host reactivity” is not only able to demonstrate the capacity of InsB:9-23-specific human CD4 T cells to initiate diabetes, but also provides a model that has the potential to revolutionize studies related to the immunopathogenesis and immunotherapies (in particular antigen-specific therapies) associated with T1D.
This humanized mouse model will allow for investigation of “pathogenicity and recruitment of human islet autoreactive T-cells, as well as identify their potentially initiating or pathogenic target beta-cell autoantigens, rendering this model uniquely suited to investigate antigen-specific immunotherapy in T1D in preclinical models in vivo” that thus far have been impossible with any other animal model, according to Tan, et al. Researchers, clinicians and patients alike are certainly eager to see what the future holds with regards to the treatment of T1D and this could be a major breakthrough in the understanding of the disease.