Allogeneic CD4 T Cells Sustain Effective BK Polyomavirus-Specific CD8 T Cell Response in Kidney Transplant Recipients
Introduction: BK polyomavirus-associated nephropathy (BKPyVAN) is a significant complication in kidney transplant recipients (KTRs), associated with a higher level of plasmatic BK polyomavirus (BKPyV) replication and leading to poor graft survival. Methods: We prospectively followed-up with 100 KTRs...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-08-01
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| Series: | Kidney International Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S246802492401708X |
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| author | Manon Dekeyser Marie-Ghislaine de Goër de Herve Houria Hendel-Chavez Romain Lhotte Ivan Scriabine Karen Bargiel Emmanuelle Boutin Florence Herr Jean-Luc Taupin Yassine Taoufik Antoine Durrbach |
| author_facet | Manon Dekeyser Marie-Ghislaine de Goër de Herve Houria Hendel-Chavez Romain Lhotte Ivan Scriabine Karen Bargiel Emmanuelle Boutin Florence Herr Jean-Luc Taupin Yassine Taoufik Antoine Durrbach |
| author_sort | Manon Dekeyser |
| collection | DOAJ |
| description | Introduction: BK polyomavirus-associated nephropathy (BKPyVAN) is a significant complication in kidney transplant recipients (KTRs), associated with a higher level of plasmatic BK polyomavirus (BKPyV) replication and leading to poor graft survival. Methods: We prospectively followed-up with 100 KTRs with various degrees of BKPyV reactivation (no BKPyV reactivation, BKPyV-DNAuria, BKPyV-DNAemia, and biopsy-proven BKPyVAN [bp-BKPyVAN], 25 patients per group) and evaluated BKPyV-specific T cell functionality and phenotype. Results: We demonstrate that bp-BKPyVAN is associated with a loss of BKPyV-specific T cell proliferation, cytokine secretion, and cytotoxic capacities. This severe functional impairment is associated with an overexpression of lymphocyte inhibitory receptors (programmed cell death 1 [PD1], cytotoxic T lymphocyte-associated protein 4, T cell immunoreceptor with Ig and ITIM domains, and T cell immunoglobulin and mucin domain-containing-3), highlighting an exhausted-like phenotype of BKPyV-specific CD4 and CD8 T cells in bp-BKPyVAN. This T cell dysfunction is associated with low class II donor-recipient human leukocyte antigen (HLA) divergence. In contrast, in the context of higher class II donor-recipient HLA (D/R-HLA) divergence, allogeneic CD4 T cells can provide help that sustains BKPyV-specific CD8 T cell responses. In vitro, allogeneic HLA-mismatched CD4 T cells rescue BKPyV-specific CD8 T cell responses. Conclusion: Our findings suggest that in KTRs, allogeneic CD4 T cells can help to maintain an effective BKPyV-specific CD8 T cell response that better controls BKPyV replication in the kidney allograft and may protect against BKPyVAN. |
| format | Article |
| id | doaj-art-3ee4a3c21cba48a1bebf6e307d0f8d8a |
| institution | DOAJ |
| issn | 2468-0249 |
| language | English |
| publishDate | 2024-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Kidney International Reports |
| spelling | doaj-art-3ee4a3c21cba48a1bebf6e307d0f8d8a2025-08-20T03:21:18ZengElsevierKidney International Reports2468-02492024-08-01982498251310.1016/j.ekir.2024.04.070Allogeneic CD4 T Cells Sustain Effective BK Polyomavirus-Specific CD8 T Cell Response in Kidney Transplant RecipientsManon Dekeyser0Marie-Ghislaine de Goër de Herve1Houria Hendel-Chavez2Romain Lhotte3Ivan Scriabine4Karen Bargiel5Emmanuelle Boutin6Florence Herr7Jean-Luc Taupin8Yassine Taoufik9Antoine Durrbach10INSERM 1186, Gustave Roussy Institute, Villejuif, France; Paris-Saclay University, Paris, France; Department of Nephrology, Center Hospitalier Régional Universitaire d'Orléans, Orléans, FranceINSERM 1186, Gustave Roussy Institute, Villejuif, France; Paris-Saclay University, Paris, FranceINSERM 1186, Gustave Roussy Institute, Villejuif, France; Paris-Saclay University, Paris, FranceLaboratory of Immunology and Histocompatibility, Saint Louis Hospital, Assistance Publique-Hôpitaux de Paris, INSERM U976 (Team 3), Paris, FranceINSERM 1186, Gustave Roussy Institute, Villejuif, France; Paris-Saclay University, Paris, FranceINSERM 1186, Gustave Roussy Institute, Villejuif, France; Paris-Saclay University, Paris, FranceUnit of Clinical Research, Henri Mondor Hospital, Assistance Publique-Hôpitaux de Paris, Creteil, France; Paris Est Creteil University, INSERM, IMRB, CEpiA Team, Creteil, FranceINSERM 1186, Gustave Roussy Institute, Villejuif, France; Paris-Saclay University, Paris, FranceLaboratory of Immunology and Histocompatibility, Saint Louis Hospital, Assistance Publique-Hôpitaux de Paris, INSERM U976 (Team 3), Paris, FranceINSERM 1186, Gustave Roussy Institute, Villejuif, France; Paris-Saclay University, Paris, FranceINSERM 1186, Gustave Roussy Institute, Villejuif, France; Paris-Saclay University, Paris, France; Department of Nephrology and Transplantation, Henri Mondor Hospital, Assistance Publique-Hôpitaux de Paris, Creteil, France; Correspondence: Antoine Durrbach, Department of Nephrology and Transplantation, INSERM 1186 Hospital Henri Mondor, 51 avenue du Maréchal de Lattre de Tassigny, 94000 Creteil, France.Introduction: BK polyomavirus-associated nephropathy (BKPyVAN) is a significant complication in kidney transplant recipients (KTRs), associated with a higher level of plasmatic BK polyomavirus (BKPyV) replication and leading to poor graft survival. Methods: We prospectively followed-up with 100 KTRs with various degrees of BKPyV reactivation (no BKPyV reactivation, BKPyV-DNAuria, BKPyV-DNAemia, and biopsy-proven BKPyVAN [bp-BKPyVAN], 25 patients per group) and evaluated BKPyV-specific T cell functionality and phenotype. Results: We demonstrate that bp-BKPyVAN is associated with a loss of BKPyV-specific T cell proliferation, cytokine secretion, and cytotoxic capacities. This severe functional impairment is associated with an overexpression of lymphocyte inhibitory receptors (programmed cell death 1 [PD1], cytotoxic T lymphocyte-associated protein 4, T cell immunoreceptor with Ig and ITIM domains, and T cell immunoglobulin and mucin domain-containing-3), highlighting an exhausted-like phenotype of BKPyV-specific CD4 and CD8 T cells in bp-BKPyVAN. This T cell dysfunction is associated with low class II donor-recipient human leukocyte antigen (HLA) divergence. In contrast, in the context of higher class II donor-recipient HLA (D/R-HLA) divergence, allogeneic CD4 T cells can provide help that sustains BKPyV-specific CD8 T cell responses. In vitro, allogeneic HLA-mismatched CD4 T cells rescue BKPyV-specific CD8 T cell responses. Conclusion: Our findings suggest that in KTRs, allogeneic CD4 T cells can help to maintain an effective BKPyV-specific CD8 T cell response that better controls BKPyV replication in the kidney allograft and may protect against BKPyVAN.http://www.sciencedirect.com/science/article/pii/S246802492401708XBK polyomavirus reactivationBK polyomavirus-associated nephropathyBK polyomavirus-specific T celldonor-recipient HLA divergencekidney transplantation |
| spellingShingle | Manon Dekeyser Marie-Ghislaine de Goër de Herve Houria Hendel-Chavez Romain Lhotte Ivan Scriabine Karen Bargiel Emmanuelle Boutin Florence Herr Jean-Luc Taupin Yassine Taoufik Antoine Durrbach Allogeneic CD4 T Cells Sustain Effective BK Polyomavirus-Specific CD8 T Cell Response in Kidney Transplant Recipients Kidney International Reports BK polyomavirus reactivation BK polyomavirus-associated nephropathy BK polyomavirus-specific T cell donor-recipient HLA divergence kidney transplantation |
| title | Allogeneic CD4 T Cells Sustain Effective BK Polyomavirus-Specific CD8 T Cell Response in Kidney Transplant Recipients |
| title_full | Allogeneic CD4 T Cells Sustain Effective BK Polyomavirus-Specific CD8 T Cell Response in Kidney Transplant Recipients |
| title_fullStr | Allogeneic CD4 T Cells Sustain Effective BK Polyomavirus-Specific CD8 T Cell Response in Kidney Transplant Recipients |
| title_full_unstemmed | Allogeneic CD4 T Cells Sustain Effective BK Polyomavirus-Specific CD8 T Cell Response in Kidney Transplant Recipients |
| title_short | Allogeneic CD4 T Cells Sustain Effective BK Polyomavirus-Specific CD8 T Cell Response in Kidney Transplant Recipients |
| title_sort | allogeneic cd4 t cells sustain effective bk polyomavirus specific cd8 t cell response in kidney transplant recipients |
| topic | BK polyomavirus reactivation BK polyomavirus-associated nephropathy BK polyomavirus-specific T cell donor-recipient HLA divergence kidney transplantation |
| url | http://www.sciencedirect.com/science/article/pii/S246802492401708X |
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