Activated human renal tubular cells inhibit autologous immune responses.

BACKGROUND: Renal proximal tubule epithelial cells (PTEC) respond and contribute to the pathological process in a range of kidney diseases. Within this disease setting, PTEC up-regulate surface antigens which may enable them to act as non-professional antigen-presenting cells and become targets for infiltrating T cells in the context of disease and allograft rejection. In order to define, for the first time, whether PTEC modulate immune responses within the autologous human system, we monitored their interaction with T and B cells in the presence of stimuli which mimic immunological signalling.
METHODS: The expression of PTEC surface antigen in response to inflammatory mediators was monitored by flow cytometry. Purified T and B lymphocyte subsets and peripheral blood mononuclear cells were cultured in the presence or absence of autologous activated PTEC, and their responses to specific activators were monitored by proliferation, cytokine secretion and surface antigen expression. Some experiments were performed in the presence of blocking antibodies to PD-L1.
RESULTS: The presence of activated primary autologous PTEC resulted in significantly decreased T- and B-cell proliferative responses, which were only partly mediated by programmed death ligand 1. This modulation was not induced by a decrease in activation markers or an increase in T regulatory cells but was accompanied by strong significant skewing of cytokine profiles. Significant decreases in gamma-interferon, interleukin-2 and tumour necrosis factor and increases in interleukin-4 were detected in the presence of PTEC, indicating that these cells induce a shift away from an inflammatory Th1 effector profile to a Th2 type profile.
CONCLUSION: Human PTEC do modulate autologous immune responses. We hypothesize that such mechanisms may have developed to help dampen inflammatory responses and macrophage activation seen within kidney interstitium in many immune-mediated kidney diseases.