Age-Related Changes in Thymic Central Tolerance.

Jayashree Srinivasan,Laura P. Hale,Nandini Singarapu,Ellen R. Richie,Lauren I. R. Ehrlich,Jessica N. Lancaster

doi:10.3389/fimmu.2021.676236

Abstract

Thymic epithelial cells (TECs) and hematopoietic antigen presenting cells (HAPCs) in the thymus microenvironment provide essential signals to self-reactive thymocytes that induce either negative selection or generation of regulatory T cells (Treg), both of which are required to establish and maintain central tolerance throughout life. HAPCs and TECs are comprised of multiple subsets that play distinct and overlapping roles in central tolerance. Changes that occur in the composition and function of TEC and HAPC subsets across the lifespan have potential consequences for central tolerance. In keeping with this possibility, there are age-associated changes in the cellular composition and function of T cells and Treg. This review summarizes changes in T cell and Treg function during the perinatal to adult transition and in the course of normal aging, and relates these changes to age-associated alterations in thymic HAPC and TEC subsets.

Highlights

Throughout life, the immune system must balance the opposing goals of mounting protective responses against diverse pathogens, while preventing a breakdown in self-tolerance
We found that CCR7 deficiency results in increased apoptosis of MHCIIhi cDC1s and reduced antigen transfer from mTECs, with a concomitant increase in cDC2 and, surprisingly, Treg induction [70]
Multiple lines of evidence presented above suggest that the perinatal thymic microenvironment is inefficient at inducing negative selection of Tconv cells, but is biased towards selection of auto reactive Tregs that are critical for suppressing autoimmunity in various tissues throughout life

Summary

Introduction

Throughout life, the immune system must balance the opposing goals of mounting protective responses against diverse pathogens, while preventing a breakdown in self-tolerance. As TECs and thymic HAPCs play critical roles in establishing central tolerance, age-related changes in the thymic microenvironment likely impact thymocyte selection, tolerance, and peripheral T cell responses throughout the lifespan.

Results

Conclusion