Glutamine modulates CD8αα+ TCRαβ+ intestinal intraepithelial lymphocyte expression in mice with polymicrobial sepsis

Objectives: CD8 alpha alpha(+) T-cell receptor (TCR) alpha beta(+) intestinal intraepithelial lymphocytes (IELs) were found to have a regulatory function in the mucosa] immune system. Glutamine (GLN) is an amino acid with immunomodulatory effects. The aim of this study was to investigate the influences of GLN on the proportion of CD8 alpha alpha(+) TCR alpha beta(+) IELs and associated inflammatory mediator gene expression in polymicrobial sepsis. Methods: Mice were randomly assigned to a normal (NC) group, a sepsis with saline (SS) group, or a sepsis with GLN (SG) group. The NC group was fed a chow diet. Sepsis was induced by cecal ligation and puncture (CLP). The SS group was administered saline, and the SG group was given 0.75 g GLN/kg body weight via a tail vein after CLP. Mice were sacrificed 12 h after CLP, and CD8 alpha alpha(+) TCR alpha beta(+) IELs were isolated for further analysis. Results: Sepsis resulted in a lower percentage of CDS alpha alpha(+) TCR alpha beta(+) IELs, and higher messenger (m)RNA expression of complement 5a receptor, interleukin (IL)-2 receptor beta, IL-15 receptor alpha, and interferon-gamma by CD8 alpha alpha(+) TCR alpha beta(+) IELs. These immunomodulatory mediator genes decreased, whereas IL-7 receptor and transforming growth factor-beta expressions increased in CD8 alpha alpha(+) TCR alpha beta(+) IELs in septic mice with GLN administration. Annexin V/7-AAD staining revealed significantly lower apoptotic rates of CD8 alpha alpha(+) TCR alpha beta(+) IELs in the SG group. Conclusion: A single dose of GLN administered after the initiation of sepsis increased the percentage of CD8 alpha alpha(+) TCR alpha beta(+) IELs, prevented apoptosis of CD8 alpha alpha(+) TCR alpha beta(+) IELs, and downregulated CD8 alpha alpha(+) TCR alpha beta(+) IEL-expressed inflammatory mediators. These results suggest that GLN influenced the distribution and cytokine secretion of the CD8 alpha alpha(+) TCR alpha beta(+) IEL subset, which may ameliorate sepsis-induced inflammatory reactions and thus mitigate the severity of intestinal epithelial injury. (C) 2013 Elsevier Inc. All rights reserved.