Figure 2.

Accumulation of exhausted T cells as possible explanation for the long-lasting effect of the anti-CD3/anti-CXCL10 combination therapy. (A) During the progressive destruction of β-cells in the RIP-LCMV-GP model the majority of islet autoantigen (LCMV-GP) specific T cells enter a state of exhaustion. (B) Upon anti-CD3 therapy the frequency of T cells is temporarily reduced and the frequency of exhausted T cells is increased. However, upon termination of the anti-CD3 antibody treatment, newly regenerated T cells are not prevented from invading the islet microenvironment. (C) In contrast, anti-CD3/anti-CXCL10 combination therapy prevents the migration of newly regenerated, functionally active T cells to the islets and results in an increased frequency of exhausted islet autoantigen-specific T cells in the islet microenvironment.