Degranulation of cytotoxic T lymphocytes in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis

Abstract

Objective: Degranulation is an essential process for maintaining cellular homeostasis; it ensures the removal of pathogen and tumor cells. The activation of cytotoxic lymphocytes results in expression of CD107a/b on cell surface and release of cytolytic proteins. The aim of this study was to investigate the internalisation of CD107a/b and the intracellular levels of IFN-γ in circulating iNKT cells, CD8+ T cells and γδ-T cells in CFS/ME patients. Furthermore, to determine Perforin, Granzyme A and Granzyme B expression in CFS/ME patients in comparison to a non-fatigued control group. Method: 35 CFS/ME patients (age 49.32 ± 2.3) and 25 non-fatigued controls (age 48.79 ± 2.5) were recruited for the study. Inclusion into the CFS/ME group was based on the 1994 Centre for Disease Prevention and Control criteria or the International Consensus Criteria. PBMCs were isolated and treated with transport inhibitors in the presence of CD107a/b antibodies, prior to 6 hours stimulation with: K562 cells, PMA/I or PHA. Cells were then stained with monoclonal antibodies specific for iNKT cells, γδ+ cells and CD8+ cells, prior to flow cytometric analysis. Result: The results demonstrated significant decreased of IFN- γ synthesis in activated total γδ-T cells; significant elevation in circulating total γδ –T and central memory expansion; and reduced iNKT cells intracellular perforin in the CFS/ME patients in comparison to the non-fatigued controls. Conclusion: This is the first study to examine degranulation in iNKTs and γδ –T cells in CFS/ME patients. Immunological dysfunctions were observed in the minor T subsets in CFS/ME patient, which may contribute to and explain the current pathogenesis of CFS/ME.