Figure 1.

Prime suspects and alleged co-conspirators at the scene of the crime: function of islet-reactive T cells and potential function(s) of non-islet-reactive T cells in insulitis. Proposed schema for islet and non-islet cell reactive T cell functions in insulitis. Representative alpha (α), beta, (β) and delta (δ); cells, and blood vessels are labeled and shown in the represented islet on the left and on the right. The islets are depicted as sources of chemoattractants/cytokines gradients (depicted in green and purple symbols, respectively) through venules with the resultant egress of lymphocytes from the pancreatic draining lymph nodes (pLN) and migration to the islets. Autoreactive CD4⁺ T cells are depicted in blue. On the left, the prime suspects, β−cell cytolytic function of islet-reactive CD8⁺ T cells (depicted in brick red) with β cell destruction depicted in brown. For both representative islets, auto-reactive CD8⁺ T cells are shown in the exocrine tissue. On the right, three potential functions of the alleged co-conspirators, non-islet-reactive T cells, on β−cell destruction by the prime suspects, are depicted. A pro-inflammation ‘potentiating’ T cell (depicted in black) with cytokine/growth factor secretion (depicted in green and purple) and increased β−cell destruction are depicted in brown. The potential suppressive function of a Treg on β−cell destruction and the potential regulatory effects of cytokines are depicted in orange. The competitive function(s) of a resource/nutrient/growth factor consuming T cells are depicted. The three proposed functions of non-islet-reactive T cells in insulitis are not necessarily mutually exclusive.