Preprint Hypothesis Version 1 Preserved in Portico This version is not peer-reviewed

Pathological T Helper Polarization Requires Pre-existing Cross-Reactive Memory T Cells

Version 1 : Received: 11 August 2021 / Approved: 12 August 2021 / Online: 12 August 2021 (08:46:55 CEST)

How to cite: Usharauli, D.; Kamala, T. Pathological T Helper Polarization Requires Pre-existing Cross-Reactive Memory T Cells. Preprints 2021, 2021080270 (doi: 10.20944/preprints202108.0270.v1). Usharauli, D.; Kamala, T. Pathological T Helper Polarization Requires Pre-existing Cross-Reactive Memory T Cells. Preprints 2021, 2021080270 (doi: 10.20944/preprints202108.0270.v1).

Abstract

Naive CD4+ T cells engage cognate peptide MHC-II complexes (pMHC-IIs) to differentiate and acquire one of several T helper (Th) fates whose specific trajectories are guided by a dynamic cytokine milieu that develops in response to antigenic entity. This physiological process is often erroneously conflated with a pathological one termed Th polarization. Using the SPIRAL model, we argue here that unlike Th fate choice, innate signaling alone is insufficient to initiate Th polarization in naive CD4+ T cells, that it instead develops from pre-existing memory CD4+ T cells that express cross-reactive TCRs, and that it inevitably leads to immunopathology.

Keywords

T helper differentiation; T helper polarization; Cross-reactivity; Regulatory T cells; Microbiota; Original Antigenic Sin

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