First Author | Kuboki S | Year | 2009 |
Journal | Am J Physiol Gastrointest Liver Physiol | Volume | 296 |
Issue | 5 | Pages | G1054-9 |
PubMed ID | 19264952 | Mgi Jnum | J:149765 |
Mgi Id | MGI:3849113 | Doi | 10.1152/ajpgi.90464.2008 |
Citation | Kuboki S, et al. (2009) Distinct contributions of CD4+ T cell subsets in hepatic ischemia/reperfusion injury. Am J Physiol Gastrointest Liver Physiol 296(5):G1054-9 |
abstractText | Helper T cells are known to mediate hepatic ischemia/reperfusion (I/R) injury. However, the precise mechanisms and subsets of CD4(+) T cells that contribute to this injury are still controversial. Therefore, we sought to determine the contributions of different CD4(+) T cell subsets during hepatic I/R injury. Wild-type, OT-II, or T cell receptor (TCR)-delta-deficient mice were subjected to 90 min of partial hepatic ischemia followed by 8 h of reperfusion. Additionally, wild-type mice were pretreated with anti-CD1d, -NK1.1, or -IL-2R-alpha antibodies before I/R injury. OT-II mice had diminished liver injury compared with wild-type mice, implicating that antigen-dependent activation of CD4(+) T cells through TCRs is involved in hepatic I/R injury. TCR-delta knockout mice had decreased hepatic neutrophil accumulation, suggesting that gammadelta T cells regulate neutrophil recruitment. We found that natural killer T (NKT) cells, but not NK cells, contribute to hepatic I/R injury via CD1d-dependent activation of their TCRs, as depletion of NKT cells by anti-CD1d antibody or depletion of both NKT cells and NK cells by anti-NK1.1 attenuated liver injury. Although regulatory T cells (Treg) are known to suppress T cell-dependent inflammation, depletion of Treg cells had little effect on hepatic I/R injury. The data suggest that antigen-dependent activation of CD4(+) T cells contributes to hepatic I/R injury. Among the subsets of CD4(+) T cells, it appears that gammadelta T cells contribute to neutrophil recruitment and that NKT cells directly injure the liver. In contrast, NK cells and Treg have little effects on hepatic I/R injury. |