Sally C. Kent, Ph.D. - UMass Diabetes Center of Excellence

The main focus of our laboratory is to understand how autoreactive T cells target insulin-producing beta cells in the pancreas in human type 1 diabetes (T1D), how this targeting may be altered or dampened, and possible environmental contributions to the progression of T1D development.

Outgrowth of T cells from an islet remnant from an isolated and handpicked islet, after culture with T cell stimulation and growth factors, from donor nPOD69, a six year old female with three years of type 1 diabetes, is shown.

Autoreactive T cell specificity and function in human Type 1 Diabetes

We, along with a great number of national and international collaborators, are now able to examine the islets from tissue donors with T1D for T cells that infiltrate the islets. Our main goal is to understand the repertoire of targets of these T cells. Recently, we showed that these islet-infiltrating T cell recognize a broad range of targets, including very newly described modified epitopes in T1D. These are epitopes that are modified by enzymes or by other processes that may be activated by cellular stress. In addition, we are working to understand the function of these islet-infiltrating T cells in terms of phenotype and effector function. It is our goal to understand the breadth of this response in order to aid in the design of therapies to alter, dampen, or turn-off the autoimmune response in individuals with T1D.

Anergy or tolerance induction in human Type 1 Diabetes

We are collaborating with investigators whose goal it is to alter, dampen, or turn-off the autoimmune response in individuals with T1D. These investigators are employing different method of introducing the epitopes, that are the targets of the T cell autoreactive response in T1D, into antigen-presenting cells in a way that causes the reactive T cells to be tolerized or suppressed (anergy). We are testing a number of these approaches with the islet-infiltrating T cells we have derived from the donors with T1D.

Enterovirus in human Type 1 Diabetes

While it is not known if environmental conditions play a role in the triggering or progression of human T1D, many investigators have focused on exposure to enteroviruses. The goal here is to determine if there is a viral contribution to T1D in order to design therapies for this. We are involved in the Network of Pancreatic Organ Donors with Diabetes (nPOD) Viral Working Group. We are working with a large, international consortia of investigators and our role is to look for immunological evidence of enterovirus exposure in islet-infiltrating T cells and pancreatic draining lymph nodes from tissue donors with T1D and controls.