Neonatal Pig Sertoli Cells Survive Xenotransplantation by Creating an Immune Modulatory Environment Involving CD4 and CD8 Regulatory T Cells
The acute cell-mediated immune response presents a significant barrier to xenotransplantation. Immune-privileged Sertoli cells (SC) can prolong the survival of co-transplanted cells including xenogeneic islets, hepatocytes, and neurons by protecting them from immune rejection. Additionally, SC survi...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2020-08-01
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| Series: | Cell Transplantation |
| Online Access: | https://doi.org/10.1177/0963689720947102 |
| _version_ | 1818504466237751296 |
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| author | Gurvinder Kaur Kandis Wright Payal Mital Taylor Hibler Jonathan M. Miranda Lea Ann Thompson Katelyn Halley Jannette M. Dufour |
| author_facet | Gurvinder Kaur Kandis Wright Payal Mital Taylor Hibler Jonathan M. Miranda Lea Ann Thompson Katelyn Halley Jannette M. Dufour |
| author_sort | Gurvinder Kaur |
| collection | DOAJ |
| description | The acute cell-mediated immune response presents a significant barrier to xenotransplantation. Immune-privileged Sertoli cells (SC) can prolong the survival of co-transplanted cells including xenogeneic islets, hepatocytes, and neurons by protecting them from immune rejection. Additionally, SC survive as allo- and xenografts without the use of any immunosuppressive drugs suggesting elucidating the survival mechanism(s) of SC could be used to improve survival of xenografts. In this study, the survival and immune response generated toward neonatal pig SC (NPSC) or neonatal pig islets (NPI), nonimmune-privileged controls, was compared after xenotransplantation into naïve Lewis rats without immune suppression. The NPSC survived throughout the study, while NPI were rejected within 9 days. Analysis of the grafts revealed that macrophages and T cells were the main immune cells infiltrating the NPSC and NPI grafts. Further characterization of the T cells within the grafts indicated that the NPSC grafts contained significantly more cluster of differentiation 4 (CD4) and cluster of differentiation 8 (CD8) regulatory T cells (Tregs) at early time points than the NPI grafts. Additionally, the presence of increased amounts of interleukin 10 (IL-10) and transforming growth factor (TGF) β and decreased levels of tumor necrosis factor (TNF) α and apoptosis in the NPSC grafts compared to NPI grafts suggests the presence of regulatory immune cells in the NPSC grafts. The NPSC expressed several immunoregulatory factors such as TGFβ, thrombospondin-1 (THBS1), indoleamine-pyrrole 2,3-dioxygenase, and galectin-1, which could promote the recruitment of these regulatory immune cells to the NPSC grafts. In contrast, NPI grafts had fewer Tregs and increased apoptosis and inflammation (increased TNFα, decreased IL-10 and TGFβ) suggestive of cytotoxic immune cells that contribute to their early rejection. Collectively, our data suggest that a regulatory graft environment with regulatory immune cells including CD4 and CD8 Tregs in NPSC grafts could be attributed to the prolonged survival of the NPSC xenografts. |
| first_indexed | 2024-12-10T21:37:28Z |
| format | Article |
| id | doaj.art-f1f27819ae014b9ca9b9cda5123192b8 |
| institution | Directory Open Access Journal |
| issn | 1555-3892 |
| language | English |
| last_indexed | 2024-12-10T21:37:28Z |
| publishDate | 2020-08-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Cell Transplantation |
| spelling | doaj.art-f1f27819ae014b9ca9b9cda5123192b82022-12-22T01:32:37ZengSAGE PublishingCell Transplantation1555-38922020-08-012910.1177/0963689720947102Neonatal Pig Sertoli Cells Survive Xenotransplantation by Creating an Immune Modulatory Environment Involving CD4 and CD8 Regulatory T CellsGurvinder Kaur0Kandis Wright1Payal Mital2Taylor Hibler3Jonathan M. Miranda4Lea Ann Thompson5Katelyn Halley6Jannette M. Dufour7 Department of Medical Education, , Lubbock, TX, USA Department of Cell Biology and Biochemistry, , Lubbock, TX, USA Department of Cell Biology and Biochemistry, , Lubbock, TX, USA Department of Cell Biology and Biochemistry, , Lubbock, TX, USA Department of Cell Biology and Biochemistry, , Lubbock, TX, USA Department of Cell Biology and Biochemistry, , Lubbock, TX, USA Department of Cell Biology and Biochemistry, , Lubbock, TX, USA Department of Medical Education, , Lubbock, TX, USAThe acute cell-mediated immune response presents a significant barrier to xenotransplantation. Immune-privileged Sertoli cells (SC) can prolong the survival of co-transplanted cells including xenogeneic islets, hepatocytes, and neurons by protecting them from immune rejection. Additionally, SC survive as allo- and xenografts without the use of any immunosuppressive drugs suggesting elucidating the survival mechanism(s) of SC could be used to improve survival of xenografts. In this study, the survival and immune response generated toward neonatal pig SC (NPSC) or neonatal pig islets (NPI), nonimmune-privileged controls, was compared after xenotransplantation into naïve Lewis rats without immune suppression. The NPSC survived throughout the study, while NPI were rejected within 9 days. Analysis of the grafts revealed that macrophages and T cells were the main immune cells infiltrating the NPSC and NPI grafts. Further characterization of the T cells within the grafts indicated that the NPSC grafts contained significantly more cluster of differentiation 4 (CD4) and cluster of differentiation 8 (CD8) regulatory T cells (Tregs) at early time points than the NPI grafts. Additionally, the presence of increased amounts of interleukin 10 (IL-10) and transforming growth factor (TGF) β and decreased levels of tumor necrosis factor (TNF) α and apoptosis in the NPSC grafts compared to NPI grafts suggests the presence of regulatory immune cells in the NPSC grafts. The NPSC expressed several immunoregulatory factors such as TGFβ, thrombospondin-1 (THBS1), indoleamine-pyrrole 2,3-dioxygenase, and galectin-1, which could promote the recruitment of these regulatory immune cells to the NPSC grafts. In contrast, NPI grafts had fewer Tregs and increased apoptosis and inflammation (increased TNFα, decreased IL-10 and TGFβ) suggestive of cytotoxic immune cells that contribute to their early rejection. Collectively, our data suggest that a regulatory graft environment with regulatory immune cells including CD4 and CD8 Tregs in NPSC grafts could be attributed to the prolonged survival of the NPSC xenografts.https://doi.org/10.1177/0963689720947102 |
| spellingShingle | Gurvinder Kaur Kandis Wright Payal Mital Taylor Hibler Jonathan M. Miranda Lea Ann Thompson Katelyn Halley Jannette M. Dufour Neonatal Pig Sertoli Cells Survive Xenotransplantation by Creating an Immune Modulatory Environment Involving CD4 and CD8 Regulatory T Cells Cell Transplantation |
| title | Neonatal Pig Sertoli Cells Survive Xenotransplantation by Creating an Immune Modulatory Environment Involving CD4 and CD8 Regulatory T Cells |
| title_full | Neonatal Pig Sertoli Cells Survive Xenotransplantation by Creating an Immune Modulatory Environment Involving CD4 and CD8 Regulatory T Cells |
| title_fullStr | Neonatal Pig Sertoli Cells Survive Xenotransplantation by Creating an Immune Modulatory Environment Involving CD4 and CD8 Regulatory T Cells |
| title_full_unstemmed | Neonatal Pig Sertoli Cells Survive Xenotransplantation by Creating an Immune Modulatory Environment Involving CD4 and CD8 Regulatory T Cells |
| title_short | Neonatal Pig Sertoli Cells Survive Xenotransplantation by Creating an Immune Modulatory Environment Involving CD4 and CD8 Regulatory T Cells |
| title_sort | neonatal pig sertoli cells survive xenotransplantation by creating an immune modulatory environment involving cd4 and cd8 regulatory t cells |
| url | https://doi.org/10.1177/0963689720947102 |
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