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

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

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...

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Bibliographic Details
Main Authors: Xavier Charmetant, Guillaume Rigault, Chien-Chia Chen, Hannah Kaminski, Jonathan Visentin, Benjamin Taton, Gabriel Marseres, Virginie Mathias, Alice Koenig, Thomas Barba, Pierre Merville, Stéphanie Graff-Dubois, Emmanuel Morelon, Julie Déchanet-Merville, Valérie Dubois, Jean-Paul Duong van Huyen, Lionel Couzi, Olivier Thaunat
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-01-01
Series:Transplant International
Subjects:
humoral response
translational science
gamma delta T cell
donor specific antibody (DSA)
B cell
Online Access:https://www.frontierspartnerships.org/articles/10.3389/ti.2025.12859/full
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Summary: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.
ISSN:1432-2277

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