New battlefields for costimulation

Abstract

Costimulation regulates the activation of naive T cells as they first encounter antigens in the secondary lymphoid organs. But recently characterized costimulatory molecules of the B7 family appear to have roles beyond initial T cell activation. New evidence shows that negative costimulators expressed by tumors and normal tissues afford local protection from T cell-mediated attack.

Figure 1.

PD-L1 mediated protection from autoimmune attack. Autoreactive T cells recognize islet-derived antigen presented by DCs in the pancreatic lymph nodes. After activation and expansion, the diabetogenic clones migrate to the islets in the pancreas. (A) Islet cells protect themselves from the autoimmune attack by expressing PD-L1. (B) Absence of PD-L1 in the islets cells as described by Keir et al. (14) allows the autoreactive T cells to invade and destroy the islet cells, initiating the autoimmune process.

Figure 2.

Tumor immune evasion assisted by macrophages. Cells of solid tumors, such as ovarian cancer described by Kryczek et al. (22), secrete IL-10 and IL-6 to induce the expression of B7-H4 in infiltrating macrophages, which in turn inhibit infiltrating T cell functions within the tumor environment. IL-10 secreted by macrophages may also inhibit T cell function.