U.S. Department of Health and Human Services
Kristin Tarbell
 

 Contact Info

 
Tel: 301-451-9360
Email: tarbellk@mail.nih.gov
 

 Select Experience

 
  • Postdoctoral Fellow and Research AssociateRockefeller University2002-2007
  • Ph.D.Stanford University2002
  • B.A.Cornell University1995
 

 Related Links

 

Kristin Tarbell, Ph.D.

Acting Section Chief, Immune Tolerance SectionDiabetes, Endocrinology, and Obesity Branch
Specialties
  • Immunology
Research Summary/In Plain Language

Research Summary

Research Goal

The goal of our research is to understand dendritic cell-mediated immune tolerance induction and how it is altered in the context of autoimmune diabetes.​

Current Research

Our research focuses on the role of dendritic cells (DCs) and regulatory T cells (Tregs) in peripheral T cell tolerance induction, and how these mechanisms are altered or deficient in an autoimmune setting.  DCs are specialized antigen-presenting cells that help determine the type of immune response that develops.  Tregs are a subset of CD4 T cells that can inhibit immune responses and help induce tolerance.

Specifically, we are studying immune tolerance primarily in the nonobese diabetic (NOD) mouse, a model of type 1 diabetes: a human T cell-mediated, organ-specific autoimmune disease in which overactive T cell responses to self-antigens expressed in the pancreatic islets cause destruction of insulin-producing beta cells.  One long-term goal of our research is to learn how to use DCs to induce autoantigen-specific tolerance for treatment of human type 1 diabetes. Below are outlined some of the areas on which we are now focusing.​

Use of steady-state DCs to enhance tolerance

If antigens are presented in the context of inflammatory signals such as toll-like receptor ligands, DCs can be activated and the result is immunity; if antigens are presented to T cells in the absence of such signals, i.e., “steady-state,” T cell tolerance results.  Tolerance can be achieve through several mechanisms including induction of either anergy (unresponsiveness) or deletion of autoreactive cells and by increasing regulatory T cells. We need to learn more about DC-mediated induction of steady-state tolerance in the environment of chronic autoimmune inflammation. However, we have now shown that, in autoimmune NOD mice, that this DC-mediated tolerance is impaired.  Specifically we have shown that one type of DC, DEC205+ cDC1, are unable to induce T cell tolerance in NOD mice, whereas another DC subset, DCIR2+ cDC2, can induce some anergy and deletion.  We are now following up on tolerogenic signals induced in T cells by the more tolerant cDC2.  Interestingly, neither DC subset from NOD mice can increase regulatory T cells.  One current direction in the lab is learn what additional signals would correct this defect and allow either induction or proliferation of regulatory T cells in NOD mice.

Autoimmune-associated alterations in innate immune signals

Innate immune activation provides rapid immune responses to pathogens such as bacterial and viral infections. But autoimmunity can ensue when innate immunity is aberrantly activated, due to a combination of environmental and genetic influences.  Viral infections and the related type 1 IFN immune response are associated with initiation of autoimmune diabetes, but the role of type 1 IFN during the chronic phase of the disease is less clear.  We have recently shown that NOD mice make more type 1 IFN in response to stimulation of the innate immune receptor TLR9.  But surprisingly, the downstream response to type 1 IFN is muted in NOD DCs.  We are now learning more about how DCs and other immune cells from NOD mice respond to innate stimuli.  In addition, we are initiating studies to measure innate responses in young adults with type 1 diabetes.

Applying our Research

The knowledge gained from our research will likely inform the design of future antigen-specific treatments for type 1 diabetes and other autoimmune diseases.​