Inflammation is believed to play a major role in the pathophysiology of acute kidney injury (AKI). identified a defect in CD4+CD25+ T cell regulatory function in patients at risk of developing AKI. Keywords: Regulatory T cell, AKI, glomerulonephritis Introduction Acute kidney injury (AKI) is usually buy 71447-49-9 the sudden loss of normal kidney function and can occur as a complication of various health issues, including but not limited to ischemic, toxic or septic insults, as well as following kidney transplant [1,2]. It is usually a severe condition that worsens the clinical outcome of affected patients, substantially increases the risk for developing chronic kidney diseases and ends-stage renal diseases, with no specific therapies available [1,3,4]. Therefore, the prevention of AKI, including devising reliable markers to prospectively identify patients at risk of developing AKI, is usually of crucial importance. Adaptive immunity is usually primarily mediated by T cells and W cells. Pathogenic T cell and W cell responses are implicated in the etiology of AKI in experimental rodent models and human renal diseases. At first, infiltration of CD3+ T cells were found in human AKI biopsies [5,6]. Since then, the role of T cells in the induction and development of AKI were examined in various experimental mouse models, including septic AKI, which reflects the renal injury following complex secondary inflammatory responses in sepsis, and aseptic ischemic AKI or nephrotoxic AKI, which reflects the renal injury following ischemia-reperfusion or induced by nephrotoxic drugs, respectively [1,7]. Although the specific findings were variable, depending on the specific models used and treatment conditions, proinflammatory CD4+ T cell-mediated response of the T helper 1 (Th1) type were found to contribute to the induction of renal injury [8], which buy 71447-49-9 was attenuated in CD4+ T cell-deficient mice in both ischemic and nephrotoxic models [9,10]. Higher infiltration of CD8+ T cells and stronger production of IFN-g by CD8+ T cells were found the post-ischemic kidneys [9,11]. Oddly enough, a subtype of T cells, termed regulatory T cells (Treg cells), was shown to have a protective role in renal injury through IL-10 mediated suppression of the innate immune system. CTLA1 Partial depletion of CD25+ Treg cells lead to increases in the infiltration of IFN-g-producing activated neutrophils and macrophages [12]. In nephrotoxic AKI, Treg cells were found to attenuate renal injury through decreasing the infiltration of macrophages [13]. The role of W cells in AKI was not entirely clear, but studies have shown that mature W cell-deficient mice were partially guarded from early renal injury [14], and W cells trafficking into kidneys were differentiating into antibody-producing plasma cells and were interfering with post-ischemic repair [15], suggesting an adverse role of B cells in AKI. Follicular helper T cells (Tfh cells) is specialized in assisting B cell differentiation and antibody production [16]. The role of Tfh cells in AKI is unknown, but increased number of circulating Tfh-like CD4+CXCR5+ T cells is associated with systemic lupus erythromatosus, one of the preceding causes of AKI, and more severe kidney damage [17,18]. These data together demonstrated the participation of T cells and B cells in the initiation, development, and repair stages of AKI. Due to the wide variety in the preceding events and causes of human AKI, the interindividual genetic variabilities and disease histories, as well as the different treatment schemes, no reliable marker currently exists to prospectively identify patients at risk of developing AKI, posing a significant difficulty in AKI prevention. Here, we designed this group-matched study to investigate the role of T cells in AKI development in patients suffering glomerulonephritis. We tracked 158 primary glomerulonephritis patients for their occurrence of AKI, and analyzed the characteristics of their adaptive immune buy 71447-49-9 system. We found that in patients that later developed AKI, peripheral blood T cell composition is shifted toward IFN-g-producing Th1-like cells. While the composition of CD4+CD25+ T cells were similar between patients that later developed AKI and patients without AKI development, in patients that later developed AKI, their CD4+CD25+ T cells secreted less regulatory cytokine IL-10, and was unable to suppress proinflammatory cytokine production by CD4+ T cells, while in patients without.