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'Personalized immune' mouse offers new tool for studying autoimmune diseases
Date:3/14/2012

an immune system, leading to graft-versus-host disease.

Dr. Sykes' model, in contrast, is able to recreate a robust and diverse human immune system, including T cells, B cells, and myeloid cells (which generate a variety of immune cells), free of immune incompatibilities.

The model is made by transplanting human bone marrow stem cells (also known as CD34+ cells), along with a small amount (approximately 1 cubic mm) of HLA-matched immature thymus tissue, into an immunodeficient mouse. (The HLA, or human leukocyte antigen, system mediates interactions among various immune cells.) The thymus tissue is implanted into the mouse's kidney capsule, a thin membrane that envelops the kidney and serves as an incubator. Within six to eight weeks, the transplanted thymus tissue is seeded by circulating human CD34+ cells (which are infused into the mouse's bloodstream), and begins generating human immune cells from the CD34+ cells.

A key to the model's success was the team's discovery that freezing and thawing the transplanted thymus tissue, as well as administering antibodies against CD2 (a glycoprotein that mediates T cell development and activation), depletes mature T cells from the tissue graft. This prevents rejection of the human CD34+ cells and graft-versus-host disease, while preserving function of the thymus tissue.

Dr. Sykes intends to use the personalized immune mouse to study type 1 diabetes. "We hope to find out what is fundamentally different about patients' immune systems, compared with those of healthy individuals, before any disease develops," she says.

The studies should also reveal more about the genetics of type 1 diabetes. "A number of HLA-associated genes have been linked to type 1 diabetes," she explains. "About a third of the population has one of more of these genes. But a much smaller percentage of the population actually develops the disease. What this means is, the HLA genes are necessary, but not sufficie
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Contact: Karin Eskenazi
ket2116@columbia.edu
212-342-0508
Columbia University Medical Center
Source:Eurekalert

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