Thread by @Plasmacellguy

Our review on peripheral T cell tolerance is now online in @NatRevImmunol

Link rdcu.be/b8LRt

I want to state a few relevant points in this 🧵

#Science #Immunology #AcademicTwitter

Most studies and perspectives focus on one mechanism of tolerance and few have seriously considered all these together in the context of T cell differentiation.

We attempted to draw a conceptual framework for the known tolerance checkpoints at each stage of the T cell lifespan

In summary, we present 6 main tolerance hallmarks:
Quiescence
Ignorance
Anergy
Exhaustion
Senescence
Death

Quiescence and Ignorance are dominant in the naive T cell stage (Yes tolerance is relevant to naive T cells)

Whereas Anergy occurs early during priming

Exhaustion is relevant during persistent costimulation, whereas we introduce senescence as a relevant tolerance hallmark

Finally, different forms of programmed death occur at virtually every stage of lymphocyte life, and serves as a critical checkpoint to restrain pathogenic inflammation.

Recall that the lymphocyte is a rare example of a cell capable of enormous damage without being transformed, therefore a T cell has to be tightly regulated via various overlapping mechanisms that we collectively label as tolerance

Genuine and profuse thanks to Dr. Steve Hedrick @ljiresearch and Dr. Chris Burns @GeiselMed for their constructive edits

Thanks to @NatRevImmunol and Daniel Utzschneider, Vassiliki Boussiotis and Pamela Ohashi for their constructive reviews which guided us and helped affinity mature this effort into much higher quality.

I truly hope the T cell immunology world would benefit from this effort to start and rethink the way we approach T cell tolerance experimentally and conceptually