CD4+ T cells, human cytomegalovirus and end-stage renal disease

CD4+ T cells are activated through their T-cell receptors, which recognize foreign antigenic peptides in the context of Major Histocompatibility Complex (MHC) II molecules [1, 2]. They have classically been regarded as facilitators of acquired immunity, providing cytokine help that aids the development of either the cellular cytotoxic CD8+ T cell (Th1) or humoral B-cell responses (Th2). However, the rapid expansion of our knowledge of cytokines and their function has resulted in the definition of further unique CD4+ T-cell subsets associated with specific immune conditions and intracellular transcription factors that drive their differentiation. It is now accepted that Th1 and Th2 differentiation are driven by the transcription factors T-bet and GATA-3, respectively [3, 4]. Th17 cells are defined by the expression of RORγt (known as RORC in humans) and RORα, express IL-23R and CCR6, secrete the cytokines IL-17 and IL-22 and are considered essential for the development of inflammatory and autoimmune disease [5–8]. Regulatory T cells (Tregs) are identified by the transcription factor FoxP3 and provide a negative buffer to immune responses through the release of suppressive cytokines such as TGFβ and IL-10 [9–11]. More recently, Th9 cells have been identified that release IL-9 and IL-10, adoptive transfer of which results in colitis and neuritis [12, 13], while Th22 cells produce IL-22 and IL-13, are defined by the transcription factors RORγt and AHR, express skin-homing receptors and are believed important in skin and mucosal pathology [14]. A summary of the above list is provided in Figure 1, but it is by no means exhaustive and there are CD4+ cell types that do not fit into these categories. However, it serves to demonstrate the complexity and plasticit