Germinal Center B Cells are Uniquely Targeted by Antibody-Suppressor CXCR5+CD8+ T Cells
Background. Alloprimed antibody-suppressor CXCR5+CD8+ T cells (CD8+ TAb-supp cells) downregulate alloantibody production, mediate cytotoxicity of IgG+ B cells, and prolong allograft survival. The purpose of this investigation was to determine which immune-cell subsets are susceptible to CD8+ TAb-sup...
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| Format: | Article |
| Language: | English |
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Wolters Kluwer
2025-02-01
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| Series: | Transplantation Direct |
| Online Access: | http://journals.lww.com/transplantationdirect/fulltext/10.1097/TXD.0000000000001742 |
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| author | Jason M. Zimmerer, PhD Sachi Chaudhari, BS Kavya Koneru, BS Jing L. Han, MD, PhD Mahmoud Abdel-Rasoul, MA Hope Uwase, MA Tai Yi, MD Christopher K. Breuer, MD Ginny L. Bumgardner, MD, PhD |
| author_facet | Jason M. Zimmerer, PhD Sachi Chaudhari, BS Kavya Koneru, BS Jing L. Han, MD, PhD Mahmoud Abdel-Rasoul, MA Hope Uwase, MA Tai Yi, MD Christopher K. Breuer, MD Ginny L. Bumgardner, MD, PhD |
| author_sort | Jason M. Zimmerer, PhD |
| collection | DOAJ |
| description | Background. Alloprimed antibody-suppressor CXCR5+CD8+ T cells (CD8+ TAb-supp cells) downregulate alloantibody production, mediate cytotoxicity of IgG+ B cells, and prolong allograft survival. The purpose of this investigation was to determine which immune-cell subsets are susceptible to CD8+ TAb-supp cell–mediated cytotoxicity or noncytotoxic suppression.
Methods. Alloprimed immune-cell subsets were evaluated for susceptibility to CD8+ TAb-supp cell–mediated in vitro cytotoxicity and/or suppression of intracellular cytokine expression. In vivo CD8-mediated cytotoxicity to wild-type germinal center (GC) B cells or wild-type CD4+ T follicular helper cells (TFH cells) was assessed in RAG1 knockout mice. The impact of in vivo adoptive transfer of CD8+ TAb-supp cells into hepatocyte or kidney transplant recipients on the quantity of lymphoid immune-cell subsets was assessed.
Results. CD8+ TAb-supp cells mediated allospecific cytotoxicity to alloprimed GC B cells but not alloprimed extrafollicular plasmablasts, marginal zone B cells, follicular B cells, or plasma cells. CD8+ TAb-supp cells did not mediate cytotoxicity to alloprimed dendritic cells, macrophages, CD4+ TFH cells, CD4+ T follicular regulatory cells, or CD4+ regulatory T cell. CD8+ TAb-supp cells did not suppress CD4+ TFH cell, T follicular regulatory cell, or regulatory T-cell cytokine expression. Adoptive transfer of CD8+ TAb-supp cells into hepatocyte or kidney transplant recipients reduced alloantibody production and the quantity of GC B cells, TFH cells, and plasma cells (but not other B-cell, T-cell, or antigen-presenting cell subsets). The reduction of TFH-cell quantity was dependent on CD8+ TAb-supp cell–mediated major histocompatibility complex-I-dependent cytotoxic killing of GC B cells.
Conclusions. The primary targets of CD8+ TAb-supp cells are GC B cells with downstream reduction of TFH and plasma cells. |
| format | Article |
| id | doaj-art-604a246d6eda475381e5a70d8095cce7 |
| institution | Kabale University |
| issn | 2373-8731 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Wolters Kluwer |
| record_format | Article |
| series | Transplantation Direct |
| spelling | doaj-art-604a246d6eda475381e5a70d8095cce72025-01-24T09:21:00ZengWolters KluwerTransplantation Direct2373-87312025-02-01112e174210.1097/TXD.0000000000001742202502000-00002Germinal Center B Cells are Uniquely Targeted by Antibody-Suppressor CXCR5+CD8+ T CellsJason M. Zimmerer, PhD0Sachi Chaudhari, BS1Kavya Koneru, BS2Jing L. Han, MD, PhD3Mahmoud Abdel-Rasoul, MA4Hope Uwase, MA5Tai Yi, MD6Christopher K. Breuer, MD7Ginny L. Bumgardner, MD, PhD81 Department of Surgery, Comprehensive Transplant Center, and the College of Medicine, The Ohio State University, Columbus, OH.1 Department of Surgery, Comprehensive Transplant Center, and the College of Medicine, The Ohio State University, Columbus, OH.1 Department of Surgery, Comprehensive Transplant Center, and the College of Medicine, The Ohio State University, Columbus, OH.1 Department of Surgery, Comprehensive Transplant Center, and the College of Medicine, The Ohio State University, Columbus, OH.3 Department of Biomedical Informatics, Center for Biostatistics, The Ohio State University, Columbus, OH.1 Department of Surgery, Comprehensive Transplant Center, and the College of Medicine, The Ohio State University, Columbus, OH.4 Center for Regenerative Medicine, The Research Institute at Nationwide Children’s Hospital, Columbus, OH.4 Center for Regenerative Medicine, The Research Institute at Nationwide Children’s Hospital, Columbus, OH.1 Department of Surgery, Comprehensive Transplant Center, and the College of Medicine, The Ohio State University, Columbus, OH.Background. Alloprimed antibody-suppressor CXCR5+CD8+ T cells (CD8+ TAb-supp cells) downregulate alloantibody production, mediate cytotoxicity of IgG+ B cells, and prolong allograft survival. The purpose of this investigation was to determine which immune-cell subsets are susceptible to CD8+ TAb-supp cell–mediated cytotoxicity or noncytotoxic suppression. Methods. Alloprimed immune-cell subsets were evaluated for susceptibility to CD8+ TAb-supp cell–mediated in vitro cytotoxicity and/or suppression of intracellular cytokine expression. In vivo CD8-mediated cytotoxicity to wild-type germinal center (GC) B cells or wild-type CD4+ T follicular helper cells (TFH cells) was assessed in RAG1 knockout mice. The impact of in vivo adoptive transfer of CD8+ TAb-supp cells into hepatocyte or kidney transplant recipients on the quantity of lymphoid immune-cell subsets was assessed. Results. CD8+ TAb-supp cells mediated allospecific cytotoxicity to alloprimed GC B cells but not alloprimed extrafollicular plasmablasts, marginal zone B cells, follicular B cells, or plasma cells. CD8+ TAb-supp cells did not mediate cytotoxicity to alloprimed dendritic cells, macrophages, CD4+ TFH cells, CD4+ T follicular regulatory cells, or CD4+ regulatory T cell. CD8+ TAb-supp cells did not suppress CD4+ TFH cell, T follicular regulatory cell, or regulatory T-cell cytokine expression. Adoptive transfer of CD8+ TAb-supp cells into hepatocyte or kidney transplant recipients reduced alloantibody production and the quantity of GC B cells, TFH cells, and plasma cells (but not other B-cell, T-cell, or antigen-presenting cell subsets). The reduction of TFH-cell quantity was dependent on CD8+ TAb-supp cell–mediated major histocompatibility complex-I-dependent cytotoxic killing of GC B cells. Conclusions. The primary targets of CD8+ TAb-supp cells are GC B cells with downstream reduction of TFH and plasma cells.http://journals.lww.com/transplantationdirect/fulltext/10.1097/TXD.0000000000001742 |
| spellingShingle | Jason M. Zimmerer, PhD Sachi Chaudhari, BS Kavya Koneru, BS Jing L. Han, MD, PhD Mahmoud Abdel-Rasoul, MA Hope Uwase, MA Tai Yi, MD Christopher K. Breuer, MD Ginny L. Bumgardner, MD, PhD Germinal Center B Cells are Uniquely Targeted by Antibody-Suppressor CXCR5+CD8+ T Cells Transplantation Direct |
| title | Germinal Center B Cells are Uniquely Targeted by Antibody-Suppressor CXCR5+CD8+ T Cells |
| title_full | Germinal Center B Cells are Uniquely Targeted by Antibody-Suppressor CXCR5+CD8+ T Cells |
| title_fullStr | Germinal Center B Cells are Uniquely Targeted by Antibody-Suppressor CXCR5+CD8+ T Cells |
| title_full_unstemmed | Germinal Center B Cells are Uniquely Targeted by Antibody-Suppressor CXCR5+CD8+ T Cells |
| title_short | Germinal Center B Cells are Uniquely Targeted by Antibody-Suppressor CXCR5+CD8+ T Cells |
| title_sort | germinal center b cells are uniquely targeted by antibody suppressor cxcr5 cd8 t cells |
| url | http://journals.lww.com/transplantationdirect/fulltext/10.1097/TXD.0000000000001742 |
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