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Myalgic Encephalomyelitis/Chronic Fatigue Syndrome as a Hyper-Regulated Immune System Driven by an Interplay Between Regulatory T Cells and Chronic Hu

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Myalgic Encephalomyelitis/Chronic Fatigue Syndrome as a Hyper-Regulated Immune System Driven by an Interplay Between Regulatory T Cells and Chronic Human Herpesvirus Infections

Full Text: https://www.frontiersin.org/article...=EMLX&utm_campaign=PRD_FEOPS_20170000_ARTICLE

Journal/Date: Front. Immunol., 21 November 2019

Abstract
Autoimmunity and chronic viral infections are recurrent clinical observations in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), a complex disease with an unknown cause. Given these observations, the regulatory CD4+ T cells (Tregs) show promise to be good candidates for the underlying pathology due to their capacity to suppress the immune responses against both self and microbial antigens. Here, we discussed the overlooked role of these cells in the chronicity of Human Herpes Virus 6 (HHV6), Herpes Simplex 1 (HSV1), and Epstein–Barr virus (EBV), as often reported as triggers of ME/CFS. Using simulations of the cross-regulation model for the dynamics of Tregs, we illustrated that mild infections might lead to a chronically activated immune responses under control of Tregs if the responding clone has a high autoimmune potential. Such infections promote persistent inflammation and possibly fatigue. We then hypothesized that ME/CFS is a condition characterized by a predominance of this type of infections under control of Tregs. In contrast, healthy individuals are hypothesized to trigger immune responses of a virus-specific clone with a low autoimmune potential. According to this hypothesis, simple model simulations of the CD4+ T-cell repertoire could reproduce the increased density and percentages of Tregs observed in patients suffering from the disease, when compared to healthy controls. A deeper analysis of Tregs in the pathogenesis of ME/CFS will help to assess the validity of this hypothesis.
The article reviews in detail the different mathematical models by which EBV, HSV-1, and HHV6 could all lead to CFS/ME through differing Treg altering mechanisms. It is concluded that any of these three viruses can lead to chronic disease states with or without the virus continuing to be active in the patient. This is strictly an academic paper that will hopefully lead to clinical interpretations, but hopefully gets us closer on the "CFS/ME as an immunological disease" research path.
 
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Cort just published a great write-up on this work and lead author Nuno Sepúlveda [SimmaronResearch]! (Full paper text also here [NCBI].)

This seems really promising to me, like it might tie in closely with Prusty's recently published paper [ImmunoHorizons], that we've been discussing in detail [PhoenixRising].

This seems like it might give an explanation for how sustained partial reactivation of HHV-6 happens. Prusty's team showed that will cause cells to secrete a serum factor signal that knocks down energy production in other cells it reaches (As previously seen with Ron's nano-needle). Plus provide generalise viral immunity in those cells, too.