[Immunopathology of acute rejection]

Acute transplant rejection may be the result of two immunologic mechanisms, T-cell-mediated and antibody-mediated processes, acting alone or together. Cell-mediated rejection occurs as T cells react to donor alloantigens which are expressed in context of MHC. The major forms of cellular rejection may affect tubulo-interstitium, arteries and glomeruli. The former type is characterized by infiltration of the interstitium and tubules with activated T cells. Typically less than 50% of the cells are CD3 (T3), while the majority are usually CD8 (T8) cells. In the tubulo-interstitial form, lymphocytes migrate from peritubular capillaries into the interstitium and into the walls of tubules (tubulitis). The arterial form is characterized by the accumulation of lymphocytes and monocytes beneath endothelial cells of arteries. Endarteritis is mediated by T cells and affected arteries are devoid of antibody or complement deposits. There are two distinctive forms of acute antibody-mediated rejection, affecting different vascular beds: arterial and peritubular capillary. The arterial form is characterized by mural necrosis and inflammation. In contrast, the peritubular capillary form may have little or variable morphologic changes; it is diagnosed by identifying C4d, a stable breakdown product of complement and an indicator of immune complex deposition, in peritubular capillary walls. C4d deposition correlates with circulating antidonor antibodies.