Transplant International (Jan 2025)

γδ T Cells’ Role in Donor-Specific Antibody Generation: Insights From Transplant Recipients and Experimental Models

  • Xavier Charmetant,
  • Xavier Charmetant,
  • Xavier Charmetant,
  • Guillaume Rigault,
  • Chien-Chia Chen,
  • Hannah Kaminski,
  • Hannah Kaminski,
  • Jonathan Visentin,
  • Jonathan Visentin,
  • Benjamin Taton,
  • Gabriel Marseres,
  • Virginie Mathias,
  • Alice Koenig,
  • Alice Koenig,
  • Alice Koenig,
  • Thomas Barba,
  • Thomas Barba,
  • Thomas Barba,
  • Pierre Merville,
  • Pierre Merville,
  • Stéphanie Graff-Dubois,
  • Emmanuel Morelon,
  • Emmanuel Morelon,
  • Emmanuel Morelon,
  • Julie Déchanet-Merville,
  • Valérie Dubois,
  • Jean-Paul Duong van Huyen,
  • Lionel Couzi,
  • Lionel Couzi,
  • Olivier Thaunat,
  • Olivier Thaunat,
  • Olivier Thaunat

DOI
https://doi.org/10.3389/ti.2025.12859
Journal volume & issue
Vol. 38

Abstract

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The generation of donor-specific antibodies (DSA) requires that alloreactive B cells receive help from follicular helper T (TFH) cells. Recent works have suggested that γδ T cells could contribute to T cell-dependent humoral responses, leading us to investigate their role in DSA generation. Analysis of a cohort of 331 kidney transplant recipients found no relation between the number of circulating γδ T cells and the risk to develop DSA. Coculture models demonstrated that activated γδ T cells were unable to promote the differentiation of B cells into plasma cells, ruling out that they can be “surrogate” TFH. In line with this, γδ T cells preferentially localized outside the B cell follicles, in the T cell area of lymph nodes, suggesting that they could instead act as “antigen-presenting cell” (APC) to prime αβ TFH. This hypothesis was proven wrong since γδ T cells failed to acquire APC functions in vitro. These findings were validated in vivo by the demonstration that following transplantation with an allogeneic Balb/c (H2d) heart, wild-type and TCRδKO C57BL/6 (H2b) mice developed similar DSA responses, whereas TCRαKO recipients did not develop DSA. We concluded that the generation of DSA is unfazed by the absence of γδ T cells.

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