Turncoat T cells, Inflammation, and Autoimmunity

Learner1

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CSMLSM

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Two different research groups have found that a special kind of T cells that are misbehaving can cause a lot of inflammation and trigger autoimmunity.

Turncoat T cells are at the core of multiple sclerosis and other inflammatory central nervous system disorders https://medicalxpress.com/news/2022-06-turncoat-cells-core-multiple-sclerosis.html
Interesting read thank you.

ME/CFS puts us at increased risk of developing self reaction from our immune system. Once part of us gets seen as not us then the autoimmune condition starts. We have a disrupted immune system that causes adaptive immune system cells to be active when they should not be and this puts us at greater risk of autoimmune diseases as well as cancer when things like EBV are affecting the immune system to persist in a latent state. IL-10 is one thing that is affected by EBV as it makes viral IL-10 when replicating and this vIL-10 binds to the same receptor as human IL-10 but does not have the same effect and causes a weaker signal when it binds instead of hIL-10. This has major regulating effects on other immune cells that are communicated to which is what part of IL-10 job is, letting other cells know what to do.

Epstein Barr Virus Interleukin 10 Suppresses Anti-inflammatory Phenotype in Human Monocytes - PMC (nih.gov)
Abstract
Epstein Barr virus (EBV) is a gamma herpes virus associated with certain malignancies and autoimmune diseases. EBV maintains latency in B cells with occasional reactivation, in part by overcoming the host immune response with viral homologs of several human proteins. EBV interleukin 10 (vIL-10), a lytic phase protein, is a homolog of human IL-10 (hIL-10). The effect of vIL-10 on human monocytes, which are one of the first immune cells to respond to infection, is not known. To understand the role of vIL-10, monocytes from peripheral blood mononuclear cells were stimulated with hIL-10 or vIL-10. Human IL-10 stimulated STAT3 phosphorylation, which is required for suppression of inflammatory responses. However, vIL-10 induced significantly lower phosphorylation of STAT3 compared to hIL-10, and was less efficient in downregulating inflammatory genes. vIL-10 significantly reduced the expression of scavenger receptor CD163 on monocytes, suggesting inhibition of M2 polarization. Furthermore, uptake of apoptotic cells was reduced in vIL-10-stimulated monocytes compared to hIL-10-stimulated monocytes. A neutralizing antibody to IL-10R1 inhibited STAT3 phosphorylation induced by either hIL-10 or vIL-10, suggesting that vIL-10 signals through IL-10R1. Interestingly, vIL-10 suppressed hIL-10-induced STAT3 phosphorylation and inhibited upregulation of suppressors of inflammatory response by hIL-10. We further show that vIL-10 levels were significantly higher in plasma samples from systemic lupus erythematosus (SLE) patients compared to matched unaffected controls. vIL-10 levels did not correlate with hIL-10 levels, but were associated with levels of IgA antibodies to EBV viral capsid antigen, which is an indirect measure of viral reactivation. We propose that the suppression of hIL-10- induced anti-inflammatory genes by vIL-10, together with an increase in inflammatory gene expression, may overcome the anti-inflammatory effects of hIL-10 and exacerbate autoimmune responses in systemic autoimmune diseases.

EBV even makes microRNA to disrupt the immune system.
An Epstein-Barr Virus MicroRNA Blocks Interleukin-1 (IL-1) Signaling by Targeting IL-1 Receptor 1 - PubMed (nih.gov)
Abstract
Epstein-Barr virus (EBV) encodes >44 viral microRNAs (miRNAs) that are differentially expressed throughout infection, can be detected in Epstein-Barr virus (EBV)-positive tumors, and manipulate several biological processes, including cell proliferation, apoptosis, and immune responses. Here, we show that EBV BHRF1-2 miRNAs block NF-κB activation following treatment with proinflammatory cytokines, specifically interleukin-1β (IL-1β). Analysis of EBV PAR-CLIP miRNA targetome data sets combined with pathway analysis revealed multiple BHRF1-2 miRNA targets involved in interleukin signaling pathways. By further analyzing changes in cellular gene expression patterns, we identified the IL-1 receptor 1 (IL1R1) as a direct target of miR-BHRF1-2-5p. Targeting the IL1R1 3' untranslated region (UTR) by EBV miR-BHRF1-2-5p was confirmed using 3'-UTR luciferase reporter assays and Western blot assays. Manipulation of EBV BHRF1-2 miRNA activity in latently infected B cells altered steady-state cytokine levels and disrupted IL-1β responsiveness. These studies demonstrate functionally relevant BHRF1-2 miRNA interactions during EBV infection, which is an important step in understanding their roles in pathogenesis.IMPORTANCE IL-1 signaling plays an important role in inflammation and early activation of host innate immune responses following virus infection. Here, we demonstrate that a viral miRNA downregulates the IL-1 receptor 1 during EBV infection, which consequently alters the responsiveness of cells to IL-1 stimuli and changes the cytokine expression levels within infected cell populations. We postulate that this viral miRNA activity not only disrupts IL-1 autocrine and paracrine signaling loops that can alert effector cells to sites of infection but also provides a survival advantage by dampening excessive inflammation that may be detrimental to the infected cell.

Here is something more related to what you posted maybe it will interest you also.
EBV-specific CD8 T lymphocytes and B cells during glatiramer acetate therapy in patients with MS - PMC (nih.gov)
Take from above-
During several chronic viral infections, virus-specific CD8 T cells become functionally exhausted. These cells are unable to mount their effector activities useful to defeat the infection.7,8 This functional impairment is associated with the expression of inhibitory receptors, which negatively regulate lymphocyte function.9

We have previously shown that disease activity is closely linked to the number of circulating CD8 T cells recognizing either lytic or latent EBV antigens.10 In the present study, we expanded the pentamers' panel used in the previous work, and we extended our investigations to provide a phenotypic and functional characterization of EBV-specific CD8 T cells.

Moreover, recent studies have revealed a substantial role for B cells in MS, which may also involve their interaction with T cells, rather than the sole production of antibodies. Thus, we broadened our study to include the characterization of B cells focusing on their expression of markers of differentiation and on their ability to interact with T cells.
 

Learner1

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During several chronic viral infections, virus-specific CD8 T cells become functionally exhausted. These cells are unable to mount their effector activities useful to defeat the infection.7,8 This functional impairment is associated with the expression of inhibitory receptors, which negatively regulate lymphocyte function.9
Good find. So, how do we untire our T cells? My cytotoxic T lymphocytes were tested and found not to be capable of killing much....
 

CSMLSM

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Good find. So, how do we untire our T cells? My cytotoxic T lymphocytes were tested and found not to be capable of killing much....
Frontiers | Expression and Functions of the CB2 Receptor in Human Leukocytes | Pharmacology (frontiersin.org)
The cannabinoid CB2 receptor was cloned from the promyeloid cell line HL-60 and is notably expressed in most, if not all leukocyte types. This relatively restricted localization, combined to the absence of psychotropic effects following its activation, make it an attractive drug target for inflammatory and autoimmune diseases. Therefore, there has been an increasing interest in the past decades to identify precisely which immune cells express the CB2 receptor and what are the consequences of such activation. Herein, we provide new data on the expression of both CB1 and CB2 receptors by human blood leukocytes and discuss the impact of CB2 receptor activation in human leukocytes. While the expression of the CB2 mRNA can be detected in eosinophils, neutrophils, monocytes, B and T lymphocytes, this receptor is most abundant in human eosinophils and B lymphocytes. We also review the evidence obtained from primary human leukocytes and immortalized cell lines regarding the regulation of their functions by the CB2 receptor, which underscore the urgent need to deepen our understanding of the CB2 receptor as an immunoregulator in humans.

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From Wiki-
Anandamide's (AEA) effects can occur in either the central or peripheral nervous system. These distinct effects are mediated primarily by CB1 cannabinoid receptors in the central nervous system, and CB2 cannabinoid receptors in the periphery.

From Wiki-
β-Caryophyllene acts as a full agonist of the Cannabinoid receptor type 2 (CB2 receptor) in rats.[6] β-Caryophyllene has a binding affinity of Ki = 155nM at the CB2 receptors in mice.[7] β-Caryophyllene has been shown to have anti-inflammatory action linked to its CB2 receptor activity in a study comparing the pain killing effects in mice with and without CB2 receptors with the group of mice without CB2 receptors seeing little benefit compared to the mice with functional CB2 receptors.[6] β-Caryophyllene has the highest cannabinoid activity compared to the ring opened isomer α-caryophyllene which may modulate CB2 activity.[8] To compare binding, Cannabinol (CBN) binds to the CB2 receptors as a partial agonist with an affinity of CB2 Ki = 126.4 nM[9] while Delta-9-Tetrahydrocannabinol binds to the CB2 receptors as a partial agonist with an affinity of Ki = 36nM.[10]
 

Learner1

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From Wiki-
Anandamide's (AEA) effects can occur in either the central or peripheral nervous system. These distinct effects are mediated primarily by CB1 cannabinoid receptors in the central nervous system, and CB2 cannabinoid receptors in the periphery.
Anandamine apparently can be increased by eating chocolate, apples, and blackberries.

https://peninsulamd.com/pah-blog/2019/4/15/how-to-nurture-your-endocannabinoid-system

Unfortunately, my immunologist thinks I have exhausted T cells, even though I do eat those foods....😉
β-Caryophyllene has been shown to have anti-inflammatory action linked to its CB2 receptor activity in a study comparing the pain killing effects in mice with and without CB2 receptors with the group of mice without CB2 receptors seeing little benefit compared to the mice with functional CB2 receptors.
"Caryophyllene, more formally-β-caryophyllene, is a natural bicyclic sesquiterpene that is a constituent of many essential oils, especially clove oil, the oil from the stems and flowers of Syzygium aromaticum, the essential oil of Cannabis sativa, rosemary, and hops."
Wikipedia

I grow rosemary and use a fair amount of it, but it hasn't helped either. I'm not in pain, typically, so maybe it doesn't apply?
 

CSMLSM

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Anandamine apparently can be increased by eating chocolate, apples, and blackberries.

https://peninsulamd.com/pah-blog/2019/4/15/how-to-nurture-your-endocannabinoid-system

Unfortunately, my immunologist thinks I have exhausted T cells, even though I do eat those foods....😉

"Caryophyllene, more formally-β-caryophyllene, is a natural bicyclic sesquiterpene that is a constituent of many essential oils, especially clove oil, the oil from the stems and flowers of Syzygium aromaticum, the essential oil of Cannabis sativa, rosemary, and hops."
Wikipedia

I grow rosemary and use a fair amount of it, but it hasn't helped either. I'm not in pain, typically, so maybe it doesn't apply?
It does not contain enough nor does many other things with Caryophyllene in when you consider other stuff in the plants that contain it and the interactions between all of it. That is why Copaiba is so good it is mostly Caryophyllene.
It is in pepper and most of the world probably eats that but we still have increases in auto immune diseases.

Medications need to be at the right dosing to work. Like say LDN needing to be a low dose to work or the opioid receptors become completely blocked and you do not get a tripling of endogenous endorphines that help with symptoms.
I have been looking for a source of Caryophyllene for 10 years approximately that I could afford and trust. Caryophyllene is in a lot of things just not enough to work is the answer to
so maybe it doesn't apply?
Same as if you took 1/16 of a codeine tablet, you would not get any pain relief and according to this situation codeine has no pain relieving ability and obviously this is not true as we know.
Unfortunately, my immunologist thinks I have exhausted T cells, even though I do eat those foods....😉
I know thats why I showed a chart showing the ability of anandamide to down regulated the activation of the T cells and that it is done via the CB2 receptor which can be activated with Caryophyllene which is a selective CB2 agonist.
 
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Learner1

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I have been looking for a source of Caryophyllene for 10 years approximately that I could afford and trust
Here you go. Better read the disclaimer.

https://trueterpenes.com/products/pure-terpene-isolates/isolates/beta-caryophyllene/
Medications need to be at the right dosing to work
People are different sizes and have different genetics which affect if and how drugs work as well as dosing needed for benefit. It's not a one size fits all thing.
Same as if you took 1/16 of a codeine tablet, you would not get any pain relief and according to this situation codeine has no pain relieving ability and obviously this is not true as we know.
A lot of ME/CFS patients can only tolerate tiny doses and have magnified effects from normal doses.
thats why I showed a chart showing the ability of anandamide to down regulated the activation of the T cells and that it is done via the CB2 receptor which can be activated with Caryophyllene which is a selective CB2 agonist
So, how are you going to safely take it? Seems like vaping it is a bad idea... How does one ne know the exact concentration and dose?
 

CSMLSM

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Here you go. Better read the disclaimer.

https://trueterpenes.com/products/pure-terpene-isolates/isolates/beta-caryophyllene/
People are different sizes and have different genetics which affect if and how drugs work as well as dosing needed for benefit. It's not a one size fits all thing.
A lot of ME/CFS patients can only tolerate tiny doses and have magnified effects from normal doses.
So, how are you going to safely take it? Seems like vaping it is a bad idea... How does one ne know the exact concentration and dose?
UNII - BHW853AU9H (fda.gov)
1657100305699.png

beta-Caryophyllene | C15H24 - PubChem (nih.gov)
1657100557304.png

1657100688995.png

People are different sizes and have different genetics which affect if and how drugs work as well as dosing needed for benefit. It's not a one size fits all thing.
Thats why I said it had to be the right dose?
Everyone has cannabinoid receptors and they do the same thing in everyone. This works on mechanistic principles of receptor and ligand, equals effect X against mechanism Y.

A lot of ME/CFS patients can only tolerate tiny doses and have magnified effects from normal doses.
I thought you might say that, but I am sure my point that I was making did not completely pass you by?

So, how are you going to safely take it? Seems like
vaping it is a bad idea... How does one ne know the exact concentration and dose?
I have consumed this in cannabis in smaller amounts over a 25 year period until I discovered what it was and found a source of higher concentration and started to consume that.
I have been vaping it and have been since the first time I tried Copaiba essential oil, which funny enough is used on diffusers in aroma therapy, so you breath it in.
I have also made a sublingual dropper with it and put it in gelatine capsules.

I now do not have any symptoms 99% of the time when I keep up with the Copaiba.
1657100876514.png

Caryophyllene /ˌkærioʊˈfɪliːn/, more formally (−)-β-caryophyllene, (BCP), is a natural bicyclic sesquiterpene that is a constituent of many essential oils, especially clove oil, the oil from the stems and flowers of Syzygium aromaticum (cloves),[3] the essential oil of Cannabis sativa, rosemary,[4] and hops.[5] It is usually found as a mixture with isocaryophyllene (the cis double bond isomer) and α-humulene (obsolete name: α-caryophyllene), a ring-opened isomer. Caryophyllene is notable for having a cyclobutane ring, as well as a trans-double bond in a 9-membered ring, both rarities in nature.

Caryophyllene is one of the chemical compounds that contributes to the aroma of black pepper.[12]
Caryophyllene has been given GRAS (generally regarded as safe) designation by the FDA and is approved by the FDA for use as a food additive, typically for flavoring.[13][14]

1657100924800.png


Caryophyllene oxide,[17] in which the alkene group of caryophyllene has become an epoxide, is the component responsible for cannabis identification by drug-sniffing dogs[18][19] and is also an approved food additive, often as flavoring.[14]
1657101069416.png


This is from the manufacturer in India of what I use-

View attachment 1657100980791.png
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Copaiba
The balsam may be steam distilled to give copaiba oil, a colorless to light yellow liquid with the characteristic odor of the balsam and an aromatic, slightly bitter, pungent taste. The oil consists primarily of sesquiterpene hydrocarbons; its main component is β-caryophyllene.[1] The oil also contains significant amounts of α-bergamotene, α-copaene, and β-bisabolene.[2]

Copaiba oil-resins extracted have been used in folk medicine dating back to the 16th century by the natives of north and northeastern Brazil. The folk remedies were administered orally or used as an ointment in the treatment of various diseases.[5] In Panama, the Yaviza people mix the resin with honey and give it to newborns to impart knowledge and ward off hexes.[6] Within the Peruvian Amazon near Iquitos, it is also used as an insect repellent.

Industry and commerce
The production of copaiba oil is socially significant to the Amazon because it represents approximately 95% of Brazil's oil-resin production industry. The Annual production of copaiba oil in the Amazon is estimated to be 500 tons/year.[7] The commercialization of copaiba as an oil or in capsule form has grown because of demand by traditional and widespread use, and is exported to other countries, including the United States, France, and Germany.[8]

The Food and Chemicals Codex lists copaiba oil as safe as a flavoring agent for foods.[9] Copaiba oil has both an acute oral and dermal LD50 exceeding 5 g/kg,[10] which classifies it as non-toxic.[11]

I hope that answers your questions :)
 

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