Interaction between T lymphocytes and kidney epithelial cells during renal allograft rejection

Cultured human renal epithelial cells were treated with the cytokines IFN-gamma and TNF-alpha and alteration in expression and function of markers including Classes I and II MHC antigens and the adhesion molecules LFA-3 and ICAM-1 was examined. It was found that a mixture of IFN-gamma and TNF-alpha induced Class II MHC antigens, up-regulated expression of Class I, LFA-3 and ICAM-1 molecules and enhanced binding of 51Cr-labeled mononuclear immune cells. However, lymphocytes failed to proliferate in response to allo-stimulation by renal epithelial cells. Lymphocytes recovered after four days in mixed culture with allogeneic renal cells were purified and re-stimulated with irradiated spleen cells for five days prior to measurement of proliferation. These lymphocytes failed to proliferate if the spleen cells were syngeneic with the renal cells used in the primary stimulation. However, if the renal cells were from a third-party donor the lymphocytes showed a normal proliferative response to the allogeneic spleen cells. It has been demonstrated that cytokine-stimulated renal epithelial cells bind, but fail to initiate proliferation of, resting allogenic lymphocytes and that activated renal cells can specifically anergise potentially graft damaging allospecific T lymphocytes.