The predominance of a naive T helper cell subset in the immune response of experimental acute pancreatitis

Pancreatology. Mar-Apr 2017;17(2):209-218. doi: 10.1016/j.pan.2017.02.011. Epub 2017 Feb 22.

Abstract

Introduction: In necrotizing acute pancreatitis (NAP), systemic inflammatory response syndrome (SIRS) and the compensatory anti-inflammatory response syndrome (CARS) decide overall outcome and mortality. In patients, low lymphocyte counts were found, but T-helper cells seemed to conversely increase. Our aim was to further categorize T-helper cells within the context of NAP induced SIRS and CARS.

Methods: NAP was induced by injection of sodium-taurocholate into the common bile duct of male BALB/c mice; sham treated animals received saline infusion. The animals were sacrificed at 6, 12, 24 and 48 h later. Lymphocytes from blood, liver and spleen were isolated and examined by flow cytometry. Staining was performed for CD4, CD8, CD19, CD45RB, CD25, CD69, and CD152. CD4+ cells were sorted for their CD45RB expression and sought for gene regulation associated to TH1/TH2 cells by quantitative RT-PCR.

Results: In NAP, CD4+ was solely increased in all compartments. CD8+ remained without substantial alterations. CD45RB showed significant expression in RBhigh in T-helper cells, confirmed by the CD45RBhigh/low ratio (Liver, 24 h: NAP 2.2, SHAM 0.6; p < 0.001). CD45RBhigh and -low cells were not associated to patterns of TH1/TH2 expression. In NAP, CCR4 expression was significantly decreased within RBhigh cells (fold change: 0.04, p < 0.05), while TLR6 showed significant overexpression (fold change: 2.36, p < 0.05).

Conclusion: T-helper cells increase in NAP, leaning towards CD45RBhigh expression. They resemble naive T-cells, in which NAP leads to expression profiles associated with an innate immune response. This suggests new findings in immunological pathomechanisms of NAP.

Keywords: CARS; CD45RB(high); Innate immunity; Lymphocyte suppression; Sepsis.

MeSH terms

  • Animals
  • Biomarkers
  • Humans
  • Lymphocyte Activation / immunology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Pancreatitis / immunology*
  • T-Lymphocytes, Helper-Inducer / classification
  • T-Lymphocytes, Helper-Inducer / physiology*

Substances

  • Biomarkers