Ischemia-reperfusion and immediate T cell responses

Abstract

The pathogenesis of ischemia-reperfusion injury (IRI) is complex and not well understood. Inflammation plays an important role in IRI, with involvement of leukocytes, adhesion molecules, chemokines and cytokines. Emerging data suggest a role of T cells as mediators of IRI both in renal and extra-renal organs. Divergent roles of T cell subsets have also been elucidated, suggesting a more complicated role of T cells in the different phases of IRI. This review presents recent evidence from various animal models that advances our understanding of the role T cells play in IRI. These findings entertain the possibility of using immunotherapeutic agents for the prevention and treatment of IRI.

Figure 1. Antigen-dependent and -independent T cell activation

Two signals are provided by APCs to activate T cells, including antigen-specific signal received as a result of binding of the T cell receptor to peptide presented by MHC molecule, and the second signal provided by costimulatory molecules such as B7-1 (CD80), B7-2 (CD86) and CD40. T cells can also be directly activated through Ag-independent pathways by cytokines, RANTES and oxygen free radicals. Complement system serves both during innate immunity, as well as a mediator of adaptive immunity by directly activating APCs and T cells. In IRI, Ag-independent pathways play an important role in T cell activation. Moreover, several proteins induced by IRI, including HSP, matrix component, inducible defensins, products of necrotic cells, as well as cytokines can activate APCs through TLR contributing to the T cells proliferation. Dendritic cells, macrophages, B cells and endothelial cells are involved in Ag presentation to T cells.