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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Frontiers Media S.A.
2025-01-01
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| Series: | Transplant International |
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| Online Access: | https://www.frontierspartnerships.org/articles/10.3389/ti.2025.12859/full |
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| author | 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 |
| author_facet | 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 |
| author_sort | Xavier Charmetant |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-0a91b43fb67642d48051803be6d93225 |
| institution | Kabale University |
| issn | 1432-2277 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Transplant International |
| spelling | doaj-art-0a91b43fb67642d48051803be6d932252025-01-29T13:49:15ZengFrontiers Media S.A.Transplant International1432-22772025-01-013810.3389/ti.2025.1285912859γδ T Cells’ Role in Donor-Specific Antibody Generation: Insights From Transplant Recipients and Experimental ModelsXavier Charmetant0Xavier Charmetant1Xavier Charmetant2Guillaume Rigault3Chien-Chia Chen4Hannah Kaminski5Hannah Kaminski6Jonathan Visentin7Jonathan Visentin8Benjamin Taton9Gabriel Marseres10Virginie Mathias11Alice Koenig12Alice Koenig13Alice Koenig14Thomas Barba15Thomas Barba16Thomas Barba17Pierre Merville18Pierre Merville19Stéphanie Graff-Dubois20Emmanuel Morelon21Emmanuel Morelon22Emmanuel Morelon23Julie Déchanet-Merville24Valérie Dubois25Jean-Paul Duong van Huyen26Lionel Couzi27Lionel Couzi28Olivier Thaunat29Olivier Thaunat30Olivier Thaunat31Centre International de Recherche en Infectiologie, INSERM U1111, Université Claude Bernard Lyon I, CNRS UMR5308, Ecole Normale Supérieure de Lyon, Univ. Lyon, Lyon, FranceDepartment of Transplantation, Nephrology and Clinical Immunology, Edouard Herriot Hospital, Hospices Civils de Lyon, Lyon, FranceLyon-Est Faculty of Medicine, Claude Bernard University (Lyon 1), Villeurbanne, FranceCentre International de Recherche en Infectiologie, INSERM U1111, Université Claude Bernard Lyon I, CNRS UMR5308, Ecole Normale Supérieure de Lyon, Univ. Lyon, Lyon, FranceDepartment of Surgery, National Taiwan University Hospital, Taipei, TaiwanDepartment of Nephrology, Transplantation, Dialysis and Apheresis, Bordeaux University Hospital, Bordeaux, FranceImmunoConcEpT, CNRS, Université de Bordeaux, UMR 5164, Bordeaux, FranceImmunoConcEpT, CNRS, Université de Bordeaux, UMR 5164, Bordeaux, FranceLaboratory of Immunology et Immunogenetics, Pellegrin Hospital, Bordeaux, FranceDepartment of Nephrology, Transplantation, Dialysis and Apheresis, Bordeaux University Hospital, Bordeaux, FranceImmunoConcEpT, CNRS, Université de Bordeaux, UMR 5164, Bordeaux, FranceFrench National Blood Service (EFS), HLA Laboratory, Décines, FranceCentre International de Recherche en Infectiologie, INSERM U1111, Université Claude Bernard Lyon I, CNRS UMR5308, Ecole Normale Supérieure de Lyon, Univ. Lyon, Lyon, FranceDepartment of Transplantation, Nephrology and Clinical Immunology, Edouard Herriot Hospital, Hospices Civils de Lyon, Lyon, FranceLyon-Est Faculty of Medicine, Claude Bernard University (Lyon 1), Villeurbanne, FranceCentre International de Recherche en Infectiologie, INSERM U1111, Université Claude Bernard Lyon I, CNRS UMR5308, Ecole Normale Supérieure de Lyon, Univ. Lyon, Lyon, FranceDepartment of Transplantation, Nephrology and Clinical Immunology, Edouard Herriot Hospital, Hospices Civils de Lyon, Lyon, FranceDepartment of Internal Medicine, Edouard Herriot Hospital, Hospices Civils de Lyon, Lyon, FranceDepartment of Nephrology, Transplantation, Dialysis and Apheresis, Bordeaux University Hospital, Bordeaux, FranceImmunoConcEpT, CNRS, Université de Bordeaux, UMR 5164, Bordeaux, France0Sorbonne Université, INSERM, UMRS 959, Immunology-Immunopathology-Immunotherapy (i3), Paris, FranceCentre International de Recherche en Infectiologie, INSERM U1111, Université Claude Bernard Lyon I, CNRS UMR5308, Ecole Normale Supérieure de Lyon, Univ. Lyon, Lyon, FranceDepartment of Transplantation, Nephrology and Clinical Immunology, Edouard Herriot Hospital, Hospices Civils de Lyon, Lyon, FranceLyon-Est Faculty of Medicine, Claude Bernard University (Lyon 1), Villeurbanne, FranceImmunoConcEpT, CNRS, Université de Bordeaux, UMR 5164, Bordeaux, FranceFrench National Blood Service (EFS), HLA Laboratory, Décines, France1Pathology Department, Necker Hospital, Assistance Publique-Hôpitaux de Paris, Paris, FranceDepartment of Nephrology, Transplantation, Dialysis and Apheresis, Bordeaux University Hospital, Bordeaux, FranceImmunoConcEpT, CNRS, Université de Bordeaux, UMR 5164, Bordeaux, FranceCentre International de Recherche en Infectiologie, INSERM U1111, Université Claude Bernard Lyon I, CNRS UMR5308, Ecole Normale Supérieure de Lyon, Univ. Lyon, Lyon, FranceDepartment of Transplantation, Nephrology and Clinical Immunology, Edouard Herriot Hospital, Hospices Civils de Lyon, Lyon, FranceLyon-Est Faculty of Medicine, Claude Bernard University (Lyon 1), Villeurbanne, FranceThe 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.https://www.frontierspartnerships.org/articles/10.3389/ti.2025.12859/fullhumoral responsetranslational sciencegamma delta T celldonor specific antibody (DSA)B cell |
| spellingShingle | 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 γδ T Cells’ Role in Donor-Specific Antibody Generation: Insights From Transplant Recipients and Experimental Models Transplant International humoral response translational science gamma delta T cell donor specific antibody (DSA) B cell |
| title | γδ T Cells’ Role in Donor-Specific Antibody Generation: Insights From Transplant Recipients and Experimental Models |
| title_full | γδ T Cells’ Role in Donor-Specific Antibody Generation: Insights From Transplant Recipients and Experimental Models |
| title_fullStr | γδ T Cells’ Role in Donor-Specific Antibody Generation: Insights From Transplant Recipients and Experimental Models |
| title_full_unstemmed | γδ T Cells’ Role in Donor-Specific Antibody Generation: Insights From Transplant Recipients and Experimental Models |
| title_short | γδ T Cells’ Role in Donor-Specific Antibody Generation: Insights From Transplant Recipients and Experimental Models |
| title_sort | γδ t cells role in donor specific antibody generation insights from transplant recipients and experimental models |
| topic | humoral response translational science gamma delta T cell donor specific antibody (DSA) B cell |
| url | https://www.frontierspartnerships.org/articles/10.3389/ti.2025.12859/full |
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