Research ArticleType 1 Diabetes

A Model for Personalized in Vivo Analysis of Human Immune Responsiveness

Science Translational Medicine  14 Mar 2012:
Vol. 4, Issue 125, pp. 125ra30
DOI: 10.1126/scitranslmed.3003481

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Personalized Research

From monogrammed towels to engraved wedding memorabilia, personalized gifts offer a way to give that special someone something truly unique. However, for all the talk of personalized medicine, translational research doesn’t always live up to this standard. For example, biomedical research is often performed in animal models that don’t recapitulate disease mechanisms as they manifest in any given human patient. Now, Kalscheuer et al. describe the development of what might be the perfect gift for some patients: “personalized immune” (PI) mice that allow individualized analysis of human immune responses.

To generate these PI mice, the authors isolated hematopoietic stem cells (HSCs) from the bone marrow of human adults and injected them along with matched fetal thymic tissue (depleted of T cells to prevent graft rejection) into immunodeficient mice. The resulting T cells in these mice were functional, displayed a diverse repertoire, and didn’t attack healthy tissues in the recipient mouse. Kalscheuer et al. then examined PI mice derived with HSCs from both healthy and type 1 diabetic individuals. The researchers found that T cells that arose from HSCs donated by subjects with type 1 diabetes were more likely to have an activated and memory phenotype than were T cells from healthy subject–derived HSCs, even though the T cells developed in a similar environment. These data suggest that there are intrinsic differences in HSCs from type 1 diabetic patients that contribute to the autoimmune pathology. Extending these studies to other diseases should provide new insights into pathogenesis and suggest new treatment strategies.