The antigen presentation function of renal tubular epithelial cells

Abstract

Renal tubular epithelial cells (TEC) have the capacity to function as antigen-presenting cells (APC). The processing of native antigen and the presentation of peptides bound to major histocompatibility complex (MHC) class II products on TEC results in engagement of the T cell antigen receptor (TCR). TEC also express a variety of adhesion molecules and cytokines which may enhance their interaction with T cells. The expression of intercellular adhesion molecules (ICAM-1) and vascular cell adhesion molecules (VCAM-1) on TEC enhances their adherence to T cells. Immune-activated TEC display and/or secrete numerous cytokines including tumor necrosis factor alpha (TNF alpha) which may provide accessory signals for T cells and upregulate TEC adhesion molecule receptors. We review the two signals required for T cell activation and suggest a model whereby T cell interaction with TEC can have two possible sequelae: (1) T cell activation or (2) T cell unresponsiveness. TEC and other parenchymal cells could potentially be important in maintaining peripheral tolerance to tissue-specific self-antigens if Ia (signal 1) and costimulatory signals (signal 2) are not induced simultaneously. Conversely, coordinate expression of signals 1 and 2 would inevitably lead to organ-specific immune injury. Studies to further elucidate the nature of T cell interactions with parenchymal cells are clearly essential for a more complete understanding of the pathogenesis of autoimmunity.