T cell exhaustion implications during transplantation

Exhaustion of lymphocyte function, particularly T cell exhaustion, due to prolonged exposure to a high load of foreign antigen is commonly seen during chronic viral infection as well as antitumor immune responses. This phenomenon has been associated with a determined molecular mechanism and phenotypic manifestations on the cell surface. In spite of investigation of exhaustion, mostly about CD8 responses toward viral infections, recent studies have reported that chronic exposure to antigen may develop exhaustion in CD4 + T cells, B cells, and NK cells. Little is known with respect to lymphocyte exhaustion during transplantation and its effect on aberrant anti-graft responses. Through a same mechanobiology observed during chronic exposure of foreign viral antigens, alloantigen persistence mediated by allograft could develop a favorable circumstance for exhaustion of T cells responding to allograft. However, to achieve better manipulation approaches of this event to reduce the complications during transplantation, we need to be armed with a bulk of knowledge with regard to quality and quantity of T cell exhaustion occurring in various allografts, the kinetics of exhaustion development, the impression of immunosuppressive agents on the exhaustion, and the influence of exhaustion on graft survival and immune tolerance.