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

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

JOURNAL=Transplant International

VOLUME=38

YEAR=2025

URL=https://www.frontierspartnerships.org/journals/transplant-international/articles/10.3389/ti.2025.12859

DOI=10.3389/ti.2025.12859

ISSN=1432-2277

ABSTRACT=<p>The generation of donor-specific antibodies (DSA) requires that alloreactive B cells receive help from follicular helper T (T<sub>FH</sub>) 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” T<sub>FH</sub>. 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 T<sub>FH</sub>. This hypothesis was proven wrong since γδ T cells failed to acquire APC functions <italic>in vitro</italic>. These findings were validated <italic>in vivo</italic> by the demonstration that following transplantation with an allogeneic Balb/c (H2<sup>d</sup>) heart, wild-type and TCRδKO C57BL/6 (H2<sup>b</sup>) 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.</p>