It is generally agreed that a subset of immune cells knows as T cells are the final orchestrators of the autoimmunity that defines T1D. In healthy individuals, functionally diverse T cell populations interact to maintain a balance within the immune system. The proper regulation of T cells is needed to limit their inappropriate proliferation and prevent autoimmune disease. Broadly, the regulatory T cell (Treg cell) is a well characterized cell that is known to keep autoimmunity in check. But many types of Treg cells regulate the differentiation and function of other T cells, especially the damage-inducing effector T cells (Teff). It is this balance that may help separate health from T1D. Education of both of these T cells is contingent upon exposure to self-proteins or auto-antigens during their lifetime, so they can properly distinguish a person’s own cells from those of outside invaders (for example, bacteria or viruses). The process by which T cells develop suppressor activity after activation by antigen remains relatively unexplored. The authors generated multiple human T cell clones specific to the T1D autoantigen called GAD65 and discovered a new suppressor T cell subgroup that lacked the classic Treg characteristic. They present evidence that this suppressor mechanism is involved in the prevention of T1D because it seemed to act as a ‘brake’ in retarding the proliferation of other harmful T cells. They also were impaired specifically in people with T1D, further suggesting their importance in T1D. These T cells also slowed diabetes development in NOD mice. These findings provide new insights into the development of antigen specific immune therapies for T1D.
Ramifications for Individuals with T1D:
Recent years have seen an extensive research effort in the area of understanding the role of suppressor T cells (Tregs) in T1D. It is becoming increasingly clear that various subsets of Tregs play important roles in the T1D disease process and the fine tuning of the activation, stability, function or expansion of these subsets could be critical in slowing or halting the disease progression. Extrapolation of the preclinical results described in this paper to the human system can offer us critical insights into the potential manipulation of this unique Treg subset in clinical trials or the utilization of this subset as a marker of efficacy of T cell targeted therapeutics.
This work was not supported by JDRF.
Investigators and Institutions:
Esther Bandala-Sanchez E, Yuxia Zhang, Simone Reinwald, James A Dromey, Bo-Han Lee, Junyan Qian, Ralph M Böhmer & Leonard C Harrison of Walter & Eliza Hall Institute of Medical Research, Parkville, Australia. Department of Medical Biology, University of Melbourne, Parkville, Australia
Bandala-Sanchez E, Zhang Y, and others. T cell regulation mediated by interaction of soluble CD52 with the inhibitory receptor Siglec-10. Nature Immunology 14, 741–748 (2013) doi:10.1038/ni.2610