Kidney disease is a common and serious problem affecting approximately 1.7 million Australians over the age of 25. The proximal tubular epithelial cells (PTEC) of the kidney are known to respond to and mediate the pathological processes of a range of kidney diseases. When these cells become perturbed during the disease state they secrete a range of pro-inflammatory cytokines which attract monocytes/macrophages, dendritic cells (DC) and lymphocytes into the kidney tissue. These in turn produce a secondary wave of cytokines which continue the inflammatory cycle and up-regulate molecules on the surface of PTEC. This enables them to behave as non-professional antigen presenting cells (AgPC) and modulate immune responses in the context of disease and allograft rejection. In this project we demonstrate that PTEC regulate DC, T cell and B cell responses in the context of the autologous human setting. When preformed blood CD1c+ DC or monocyte derived DC (MoDC) were co-cultured with interferon-γ (IFN-γ) activated PTEC, the CD1c+ DC and MoDC were immature and less effective in stimulating allogeneic T cell responses. The IFN-γ activated PTEC also down-regulated autologous CD4+ T cell responses and significantly compromised the antibody producing function of autologous B cells. To identify the mechanisms responsible for these immune modulations, we investigated molecules produced by PTEC within an IFN-γ induced inflammatory micro-environment. These activated PTEC expressed elevated levels immuno-regulatory of soluble human leukocyte antigen –G (sHLA-G), programmed cell death ligand-1 (PD-L1) and indoleamine-2,3- dioxygenase (IDO) which may enable then to interact with immune cells in the context of nonprofessional AgPC. Blocking experiments for each of these molecules have identified mechanisms of autologous PTEC regulating immune cell phenotype and function. The sHLA-G secreted by PTEC was partially responsible for the down-regulation of MHC-II on autologous MoDC. The expression of IDO and PD-L1 by PTEC were partly responsible for the elevated levels of PD-L1 expression on MoDC and down-regulated the allogeneic CD4+ T cell response inducing function of these cells. The IDO and sHLA-G expressed by PTEC also had an autocrine effect on the up-regulation of molecules which then induced autologous MoDC to secrete elevated levels of anti-inflammatory cytokine IL-10. IDO and sHLA-G expressed on PTEC were partially responsible for down-modulating the number of autologous B cells capable of secreting IgM antibody, whilst PD-L1 expression on PTEC played a partial role in the regulation of both IgM and IgG antibody levels from autologous B cells. Collectively, all these results suggest that autologous PTEC down-regulate DC, T cell and B cell responses, which may then control ongoing inflammation and prevent the progression of kidney disease.