Journal
AMERICAN JOURNAL OF TRANSPLANTATION
Volume 16, Issue 4, Pages 1079-1085Publisher
WILEY
DOI: 10.1111/ajt.13645
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Funding
- NHLBI NIH HHS [T32 HL007776, R01 HL113931, R01HL113931, R01 HL094601, R01HL094601] Funding Source: Medline
- NIAID NIH HHS [P01 AI116501, 1P01AI116501] Funding Source: Medline
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De novo induction of organized lymphoid aggregates at nonlymphoid sites has been observed in many chronic inflammatory conditions where foreign antigens such as infectious agents, autoantigens or alloantigens, persist. The prevailing opinion in the field of transplantation is that lymphoid neogenesis within allografts is detrimental to the establishment of immune tolerance. These structures, commonly referred to as tertiary lymphoid organs (TLOs), are thought to contribute to graft rejection by generating and propagating local alloimmune responses. However, recent studies have shown that TLOs rich in regulatory Foxp3(+) cells are present in long-term accepting allografts. The notion that TLOs can contribute to the local downregulation of immune responses has been corroborated in other chronic inflammation models. These findings suggest that contrary to previous suggestions that the induction of TLOs in allografts is necessarily harmful, the induction of tolerogenic TLOs may prove advantageous. In this review, we discuss our current understanding of how TLOs are induced and how they regulate immune responses with a particular focus on alloimmunity. This review discusses the current understanding of the induction of tertiary lymphoid organs in transplanted grafts and their contribution to the regulation of alloimmune responses.
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