Our Faculty : Primary Faculty

Allison L. Bayer, Ph.D.

Current Research Interests
Host environment is often an overlooked hurdle that needs to be understood in order to have successful therapies without the need for chronic immunosuppression. Many clinical trials for T1D patients are utilizing immunomodulation therapies that may favor T regulatory (Treg) expansion and temper Teff responses, but their efficacy has been limited in magnitude and duration. Tolerance induction protocols in transplant setting also require therapies that favor Treg expansion/stimulation, while inhibiting alloreactive Teff responses. Our past studies have addressed key questions of how to develop strategies that facilitate long-term engraftment and function of Treg therapeutic infusions. Treg immunotherapy in autoimmune setting poses more challenges given chronic inflammation could create a non-supportive environment for Treg engraftment and persistence. Recent studies by others showed that Treg depletion releases bio-available IL-2 resulting in NK subset producing IFN and initiates diabetic lesions in NOD mice, exemplifies the need to consider the role NKs play in disease progression and how alterations in NK subsets are contributing to the rebounding environment in development of novel therapies for T1D.

T regulatory cells (Tregs) inhibit self and allogeneic immune responses making these cells attractive for novel cell-based therapy approaches to promote tolerance and control autoimmune diseases, including type 1 diabetes (T1D).

Currently, Treg therapy is hindered by the inability to generate sufficient number of cells to inhibit desired immune response(s) and achieve stable Treg engraftment. We have recently identified critical factors for successful adoptive Treg cell therapy: 1) generation of peripheral space for engraftment/persistence of infused Tregs, 2) overcoming competition from endogenous Tregs, 3) provision of IL-2 to support survival/proliferation of adoptively transferred Tregs and 4) availability of relevant antigens. Despite this understanding, Treg engraftment is still hampered in diabetic compared to prediabetic NOD mice. This is likely related to an altered immune compartment following immunomodulation that cannot fully support the Treg compartment in these diabetic mice and continues to represent an obstacle to successful Treg therapy. The interplay of adaptive and innate immune system is often overlooked and the role natural killer (NK) cells in this interplay have only recently been appreciated. NK cells play important roles in immune defense, surveillance, and homeostasis. However, NK subsets remain poorly understood in mice. Furthermore, there are conflicting reports involving NK cells in T1D, as well as other autoimmune models, which could be related to the poor understanding of functional NK subsets in mice. The challenge is to resolve the inflammatory roles of NK cells with their regulatory roles in autoimmunity. One of the primary goals of the lab is to identify NK functional subsets with effector and regulatory properties using the NOD mouse model. This research is designed to test the hypothesis that in conditions of autoimmunity, NK cells are inflammatory, which may promote unfavorable environment for Treg cells. To examine our hypothesis, we aim to define which NK cell subset(s) are activated or altered in the autoimmune setting using the NOD mouse model of spontaneous autoimmune diabetes and investigate whether treating NOD mice with immunomodulation, which depletes T-cells including Tregs, leads to different representation of NK subsets during disease progression. These studies would help determine the role of NK cells in conditions of autoimmunity and will allow for the development of improved strategies for the treatment of T1D where the interplay innate and adaptive immunity has been underappreciated in the design of novel combinatorial therapies.

Research Profile