Treg-Rich Organized Lymphoid Structures That Develop In Spontaneously Accepted Murine Renal Allografts Have Thymic-Like Characteristics

Abstract

Introduction: Novel lymphoid structures identified within the parenchyma of kidney allografts are associated with the induction of spontaneous or active immune tolerance. They appear to be distinct from classic tertiary lymphoid structures and are rich in regulatory T cells (Tregs) thus, have been named Treg-rich Organized Lymphoid Structures or TOLs. It is possible that TOLs promote tolerance by regulatory of deletional mechanisms as in a thymus. Here, we determine whether TOLs have thymic-like characteristics by phenotyping the antigens expressed within TOLs. Many markers such as Aire or Foxn1 were previously thought to be unique to the thymus. However, they have recently been found in other cells or tissues in the periphery. Therefore, we have examined the simultaneous expression of a number of markers, which together are thought to define the thymus.

Methods: We used the DBA/2J kidney to C57/B6 mouse transplant system which consistently results in spontaneous kidney allograft acceptance and the development TOLS was studied. Immunohistochemistry staining of the grafts, as well as NanoString analysis of mRNA transcripts from grafts was used to assess thymus-like features6 post-transplant when TOLS are generally found to be mature.

Conclusion: The simultaneous expression of Foxn1 and Aire, and the presence of an ex- panding double-positive T cell infiltration suggest that TOLs have features characteristic of thy- mus.