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 (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 <i>in vitro</i>. These findings were validated <i>in vivo</i> 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.
Authors
- Jean–Paul Duong Van Huyen (ORCID: https://orcid.org/0000-0002-3051-2141)
- Lionel Couzi (ORCID: https://orcid.org/0000-0002-9213-6196)
- Guillaume Rigault
- Stéphanie Graff‐Dubois (ORCID: https://orcid.org/0000-0001-7273-3930)
- Julie Déchanet‐Merville (ORCID: https://orcid.org/0000-0001-7521-9531)
- Thomas Barba (ORCID: https://orcid.org/0000-0003-1281-0433)
- Pierre Merville (ORCID: https://orcid.org/0000-0001-8987-2929)
- Hannah Kaminski (ORCID: https://orcid.org/0000-0003-1604-3825)
- Valérie Dubois (ORCID: https://orcid.org/0000-0002-1169-7697)
- Benjamin Taton (ORCID: https://orcid.org/0000-0001-9609-8652)
- Jonathan Visentin (ORCID: https://orcid.org/0000-0003-3795-8979)
- Emmanuel Morelon
- Gabriel Marsères (ORCID: https://orcid.org/0000-0002-9200-2454)
- Olivier Thaunat (ORCID: https://orcid.org/0000-0002-3648-8963)
- Xavier Charmetant (ORCID: https://orcid.org/0000-0002-2162-5873)
- Alice Koenig (ORCID: https://orcid.org/0000-0003-4358-9719)
- Chien‐Chia Chen (ORCID: https://orcid.org/0000-0002-1282-976X)
- Virginie Mathias
Institutions
- Université Claude Bernard Lyon 1 (FR)
- École Normale Supérieure de Lyon (FR)
- Hôpital Necker-Enfants Malades (FR)
- Centre National de la Recherche Scientifique (FR)
- Université de Bordeaux (FR)
- Inserm (FR)
- Centre Hospitalier Universitaire de Grenoble (FR)
- Centre Hospitalier Universitaire de Bordeaux (FR)
- Sorbonne Université (FR)
- Assistance Publique – Hôpitaux de Paris (FR)
- National Blood Transfusion Service (NG)
- Hospices Civils de Lyon (FR)
- Immunology from Concept and Experiments to Translation (FR)
- Hôpital Pellegrin (FR)
- Pitié-Salpêtrière Hospital (FR)
- Hôpital Edouard Herriot (FR)
- Établissement Français du Sang (FR)
- National Taiwan University Hospital (TW)
- Centre International de Recherche en Infectiologie (FR)
- Immunologie - Immunopathologie - Immunothérapie (FR)
Publication Details
- Journal
- Transplant International
- Published
- 2025-01-29
- DOI
- https://doi.org/10.3389/ti.2025.12859
- Citations
- 3
- Primary Topic
- T-cell and B-cell Immunology
- Type
- article
- Field-Weighted Citation Impact
- 2.39
Funders
- Agence Nationale de la Recherche
- Fondation pour la Recherche Médicale
- Hospices Civils de Lyon
- Etablissement Français du Sang