Clonal expansion of hematopoietic precursors is something that we see generally as people age [1]. Rather than positing a beneficial role for clonal expansion of cytotoxic T cells, my null hypothesis would be that this clonal expansion is simply another marker of aging.
Very possible and future experiments should probe this hypothesis too. We should never forget that the very beginnings of immunotherapy were paradoxes themselves (e.g. infecting someone with a disease to control cancer). Our immune system, like many other complex non-linear systems, have been known to behave unpredictably at local levels while behaving predictably at a global level.
If you have not already read it, this is a fascinating review of the paradoxical progress of modern immunotherapy (cancer centric) - https://www.sciencedirect.com/science/article/pii/S235230421...
That disregards the possibility that certain clonal expansions could be beneficial. General clonal expansion may be correlated with aging, but some clonal expansion may concern extended longevity.
Yes, cytotoxicity is the ability to destroy cells. Most CD4 T cells are not cytotoxic, regardless of the host's age. In the Supercentenarians studied here, it was observed that the majority of their CD4 T cells were cytotoxic, which is a very surprising result.
Having more cytotoxic CD4 T's could give the immune system better ability to destroy invaders or cancer cells.
Even more surprising is that a large percentage of these mutant CD4 T's are clonal, all traceable back to one individual (T cell) that mutated.
It's been shown that supercentenarians enjoy resistance to disease over their entire lives. This research shows that may be due to their unique immune systems.
With full knowledge I am being an armchair statistician, wouldn't it be difficult to tell the difference between supercentenarians having extraordinary resistance to disease and supercentenarians being the ones who got lucky? Perhaps getting diseases is bad for your longevity!
These are not mutually exclusive possibilities: "a large percentage of these mutant CD4 T's are clonal, all traceable back to one individual (T cell) that mutated."
Wow, amazing! I don't know biology, so forgive my ignorant question:
Can these special t cells be transferred via a (blood?) transfusion? So they could clone themselves in a new person?
That could be one potential consequence but this publication just lays out the observation and clearly states this at the end - "It should be noted, however, that antigens recognized by clonally expanded TCRs are not known, and further work is required to characterize CD4 CTLs in supercentenarians." IOW, the actual characteristics of the T-cells in this sampled population is not known.
As frustrating as it sounds, more experiments are needed to say with certainty what is correlated, what is causal etc.
Ooh, that observation that the antigens are not known sounds like a really promising field for analysis and discovery tools. Reverse engineering the antigens from the cells that have evolved to recognise them.
A molecular biologist friend said "there is a super clever way to do it using phage screens", and pasted this link with some "limited info": https://en.wikipedia.org/wiki/PhIP-Seq
1 = https://en.wikipedia.org/wiki/Clonal_hematopoiesis