Lymphoid Neogenesis and Tertiary Lymphoid Organs in Transplanted Organs.

Alice Koenig,Olivier Thaunat

doi:10.3389/fimmu.2016.00646

Abstract

The progressive organization of immune effectors into functional ectopic lymphoid structures, named tertiary lymphoid organs (TLO), has been observed in many conditions in which target antigens fail to be eliminated by the immune system. Not surprisingly, TLO have been recurrently identified in chronically rejected allografts. Although significant progress has been made over the last decades in understanding the molecular mechanisms involved in TLO development (a process named lymphoid neogenesis), the role of intragraft TLO (if any) in chronic rejection remains elusive. The prevailing dogma is that TLO contribute to graft rejection by generating and propagating local humoral and cellular alloimmune responses. However, TLO have been recently observed in long-term accepting allografts, suggesting that they might also be able to regulate alloimmune responses. In this review, we discuss our current understanding of how TLO are induced and propose a unified model in which TLO can play deleterious or regulatory roles and therefore actively modulate the kinetics of chronic rejection.

Highlights

THE CHALLENGE OF CHRONIC REJECTION IN TRANSPLANTATIONVital organ failure is a life-threatening condition where a vital organ does not perform its expected function
These peculiarities suggest that the local immune response that develops in intragraft tertiary lymphoid organs (TLO) might be less tightly regulated than in secondary lymphoid organs and are more aggressive
Since grafts in which TLO were harboring germinal center reactions had a shorter life expectancy (Figure 2), we have proposed that lymphoid neogenesis could play a detrimental role during chronic rejection [8]

Summary

INTRODUCTION

Vital organ failure is a life-threatening condition where a vital organ (i.e., kidney, heart, liver, or lung...) does not perform its expected function. Comparing the cellular composition of TLO of chronically rejected grafts with one of the secondary lymphoid organs, we observed a drastic increase in the percentage of activated and memory CD4+ T cell in intragraft TLO and a symmetric decrease in T regulatory subsets (IL-10-producing Tr1 cells and Foxp3pos Tregs) in both a murine experimental model and human samples [33, 35] These peculiarities suggest that the local immune response that develops in intragraft TLO might be less tightly regulated than in secondary lymphoid organs and are more aggressive.

Key findings

CONCLUSION