What makes the kidney so tolerant?
Paolo Molinari, Paolo Cravedi
Paolo Molinari, Paolo Cravedi
Published August 15, 2024
Citation Information: J Clin Invest. 2024;134(16):e183501. https://doi.org/10.1172/JCI183501.
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Commentary

What makes the kidney so tolerant?

Abstract

Various organ allografts differ in their propensity to be spontaneously accepted without any immunosuppressive treatment. Understanding the mechanisms behind these differences can aid in managing alloimmune responses in general. C57BL/6 mice naturally accept DBA/2J kidney allografts, forming tertiary lymphoid organs containing regulatory T cells (rTLOs), crucial for graft acceptance. In this issue of the JCI, Yokose and colleagues revealed that rTLOs promote conversion of cytotoxic alloreactive CD8+ T cells into exhausted/regulatory ones, through an IFN-γ–mediated mechanism. Their study provides insights into tolerance development that could help promote the acceptance of grafts at higher risk of rejection.

Authors

Paolo Molinari, Paolo Cravedi

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Figure 1

Regulatory T cell–rich tertiary lymphoid organs have a role in kidney transplant tolerance and rejection.

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Regulatory T cell–rich tertiary lymphoid organs have a role in kidney tr...
(A) Regulatory T cell–rich tertiary lymphoid organs (rTLOs) form in the context of a kidney transplant that is tolerated by the recipient. These structures contain various types of T lymphocytes that, through the release of IFN-γ, promote the conversion of alloreactive CD8+ T cells into exhausted and then regulatory cells. (B) In contrast, kidneys that undergo rejection do not form rTLOs, but instead show diffuse and unorganized lymphocytic infiltrates, primarily composed of alloreactive CD8+ T cells, and to a lesser extent, exhausted CD8+ T cells.