Thread by @fitterhappierAJ

A stepwise depiction of phenotypes associated with poor outcomes.

DeCandia claims Tn cells more diverse & fit, leading to protection

Brodin claims a degree of energy consumption causing poor outcomes

I claim Naive/Stem cell T cells act as "cytokine sinks" for exuberance

https://twitter.com/VirusesImmunity/status/1499022862509821954

I implicate a feed-forward model of T cell differentiation and death, with a canonically paired negative feedback loop as is prototypically seen with natural feedforward control models. This negative feedback loop has ramifications.

So while Tn will quell exuberant function, Teff/Tem will deplete Tn/scm more rapidly if they interact in Lymphoid tissue. The T cells act as a quorum and Tem can slough off the Tn

Why you see depletion in LC; bystander activation and increased sloughing thanks to colocalization

They all interact together, as is known with T cells, but now we have a clean model. While the Tscm "soak" the exuberance, it causes them to age. The feed-forward controller has a reciprocal effect via the negative feedback loop in the dotted line.

Enjoy.

This has obvious ramifications for the prospect of reinfections, as I mentioned in 2020

There was not a simple narrative for this finding back when I made it so it was not published, but now covid has given the model a raison d'etre

https://twitter.com/fitterhappierAJ/status/1297352624765894656

This will be published within a week.

I'll post it for you all to read.

It's very digestible.