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Following almost 30 years of intensive research, initiated by the observation that Type 1 diabetes development is associated with a characteristic pancreatic immune cell infiltrate, a picture is emerging of which of the diverse effector arms of the immune system are involved in β-cell destruction. Like any chronic pathology, there is considerable complexity, and our ability to model the disease is hampered by a lack of ready access to the target organ and limited longitudinal analyses. However, it seems that putative pathways can start to be ruled in and out, in part as a result of focused mechanistic studies that make use of new technologies, and in part through analysis of the outcomes of clinical trials of new agents aimed at halting the disease process. The picture that emerges suggests a pathway to prevention that may require combinations of therapeutic agents that target different aspects of the immune system and will need to be used with due attention to their risk-benefit profiles. [ABSTRACT FROM AUTHOR]

Studies on physiology and pathology as they relate to the immune system draw heavily upon rodent models. With the increasing impetus provided by initiatives in translational medicine, the demand for ever more sophisticated, ‘humanized’ murine models is greater than ever. However, the design and implementation of studies in such mice is far from trivial. Here we provide a technical perspective on the increasing interest in developing humanized mice. We give examples of primary data starting with the routine procurement of human donor material, through CD34+ cell purification prior to engraftment to injection into immunocompromised mice. Our goal is to provide practical advice to the many investigators who may be commencing or considering such studies. [ABSTRACT FROM AUTHOR]