An acute cellular rejection is most commonly seen within the initial months after transplantation and is heralded by an elevation of serum creatinine levels followed by clinical signs of renal failure. Histologically, there may be extensive interstitial mononuclear cell infiltration and edema as well as mild interstitial hemorrhage.
As might be expected, immunoperoxidase staining reveals both CD4+ and CD8+ lymphocytes, and these cells express markers of activated T cells, such as the α chain of the IL-2 receptor. Glomerular and peritubular capillaries contain large numbers of mononuclear cells that may also invade the tubules, causing focal tubular necrosis.
In addition to causing tubular damage, CD8+ cells may also injure vascular endothelial cells, causing a so-called endothelitis. This form of cell-mediated vascular damage is limited to the endothelium and is distinct from the antibody-mediated vasculitis described later.
The affected vessels have swollen endothelial cells, and at places the lymphocytes can be seen between the endothelium and the vessel wall. The recognition of cellular rejection is important because, in the absence of an accompanying arteritis, patients promptly respond to immunosuppressive therapy.
Cyclosporine, a widely used immunosuppressive drug, is also nephrotoxic, and hence the histologic changes resulting from cyclosporine may be superimposed.
See also
acute rejection