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mTORC1 complex determines T-cell development


Senior Member
I've not been here for a while, due to unrelated tasks, so I may have missed some previous discussions. (For friends who worry, this is not a health problem. I'm actually a little better.)

However, when I see research that affects T-cell types, metabolism and immune function I can hardly ignore it.

This article just appeared on Medical Xpress.

Standard mainstream medicine looks for autoantibodies to detect autoimmune diseases. These are produced by B-cells and plasma cells. T-cells tend to be neglected, even though there are plenty of papers describing cases in which T-cells invade tissues where they are not normally found in healthy people. For some time I've been playing with the hypothesis that autoantibodies are often the result of immune attack on a category of host cells, not the cause. By using autoantibody levels as diagnostic criteria we may have made it impossible to find the cause, or at least complicated searches for etiology.

As for testing whether your T-cells are conventional alpha-beta or unconventional gamma-delta, that just doesn't happen in typical medicine. These are the kind of lacunae in medical research thinking I've been looking for over a period of years. It became obvious years ago that doing more of the same was not going to address the causes of many medical problems, and not just those that end up on this forum.

This could be a breakthrough.


Senior Member

The problem with studies of HIV is the wide range of immune dysfunction it causes. You are ultimately dealing with the complete collapse of immune function. I'm sure that mTORC-1 is affected, the problem is teasing out individual causes and effects.

My position on human retroviruses in general is that all humans are infected with very slow retroviruses. A few are really ancient, and probably associated with the rather strange origin of placental mammals in parallel lineages. I'm speculating that this was an example of horizontal transmission of genetic information which started as a STD in one egg-laying species. Sex with other species is unlikely, but predation and scavenging, or spread via feces is not.

Other retroviruses are more recent, thousands of years ago rather than millions.

I've changed my opinion on the origin of HTLV-1 and HTLV-2. I now believe these originated in large mammals mostly driven to extinction when humans entered the Americas. Extinctions make it hard to trace lineages, but we have the peculiar fact that some people in the Americas have coevolved with HTLV-2 to the point that it rarely presents health problems. (This does not mean it is entirely benign.) This process of adaptation took time, probably longer than contact with Europe and Africa would allow. We now know of HTLV-1 found in a mummy at high altitude in South America long predating European contact. At first I discounted this.

Other retroviruses probably date to human domestication of large mammals in Eurasia. Again, we are talking about thousands of years, not millions. Coevolution of humans and these retroviruses is incomplete, but they are so widespread that we consider the resulting problems either extremely rare, when rapidly fatal, or the result of normal aging. Populations never exposed to these typically suffered around 85% mortality over a century or so after contact with Europeans and their domestic animals. This could easily have been attributed to other diseases, since either immune dysfunction, neurological disease or cancer would be expected results. The time between infection and appearance of symptoms (latency) is simply too long for most people to make the connection without modern tests.

HIV-1 appears to have originated in the middle of the Congo at a time when horrific changes were taking place, as detailed in King Leopold's Ghost. This is precisely the kind of situation in which epidemics originate. The history matches phylogenetic reconstructions based on genetic variants and pointing to around 1910.

I discount theories of origin at the time polio vaccines reached this region, because nobody at the time anticipated that reuse of needles would spread a disease worse than polio with a latency of 10 years. It still takes a long time for some people to catch on about reusing needles. Spreading an existing disease can look a lot like an origin.

HCMV is more interesting for research because it typically leads to infections that hosts tolerate. It is a herpes virus, HHV-5. All these viruses have mechanisms for injecting genetic material that are difficult for host cells to avoid, and do not depend on precise sequences. This is a case where I think it likely we will be able to follow cause and effect to discover detailed mechanisms by which the virus fights host immune systems to a draw. A small tweak might allow host immune systems to win. What is more I doubt that any of us would be worse if we were cured of HCMV infections, or HSV, EBV or VZV or HHV-6a. I'm sure many would volunteer for an experiment.

This is where we run into a Catch-22: because these are seldom fatal infections, there are real ethical objections to performing experiments on humans. Research funding for infections not known to be lethal is also weak.

In the abstract it would make sense to study easier infections first, before you tackle a hydra monster like HIV.