CD4hiCD8low Double-Positive T Cells Are Associated with Graft Rejection in a Nonhuman Primate Model of Islet Transplantation
Peripheral CD4/CD8 double-positive (DP) T cells are associated with autoimmune disorders, cancer, and viral infection. However, the relationship between organ transplantation and DP T cells is unclear. Here, we examined the functional characteristics of peripheral DP T cells and analyzed their signi...
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| Format: | Article |
| Language: | English |
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Wiley
2018-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2018/3861079 |
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| author | Yun Jung Choi Hi-Jung Park Hye Jin Park Kyeong Cheon Jung Jae-Il Lee |
| author_facet | Yun Jung Choi Hi-Jung Park Hye Jin Park Kyeong Cheon Jung Jae-Il Lee |
| author_sort | Yun Jung Choi |
| collection | DOAJ |
| description | Peripheral CD4/CD8 double-positive (DP) T cells are associated with autoimmune disorders, cancer, and viral infection. However, the relationship between organ transplantation and DP T cells is unclear. Here, we examined the functional characteristics of peripheral DP T cells and analyzed their significance with respect to islet graft rejection in a nonhuman primate model of islet transplantation. DP T cells were functionally equivalent to conventional CD4 and CD8 T cells in terms of helper and cytotoxic activity, respectively. DP T cells expressed high levels of CXCR5 and PD-1 and secreted IFN-γ, IL-4, and IL-21 in amounts equivalent to those secreted by CD4 or CD8 T cells; also, they produced large amounts of granzyme B and perforin. In addition, under steady-state conditions, DP T cells expressed eomesodermin (Eomes) and promyelocytic leukemia zinc finger (PLZF) proteins, both of which act as transcription factors in innate/memory-like T cells. The number of peripheral DP T cells in the islet transplantation model was high in the group that experienced graft rejection; this was not the case in the long-term survival group. Interestingly, numbers of effector memory T cells (TEM) within the DP T cell population increased significantly during islet graft rejection, as did those of TEM within the cytotoxic CD8 T cells. Furthermore, the most conspicuous of which was the increase of CD4hiCD8low T cell subpopulation at that point. Taken together, the data suggest that peripheral DP T cells showing an innate/memory-like phenotype have both helper and cytotoxic activity in vitro and that they may act as a novel biomarker for graft rejection after islet transplantation. |
| format | Article |
| id | doaj-art-d09d01f2b2c04db1b67176e61bd49494 |
| institution | OA Journals |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2018-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-d09d01f2b2c04db1b67176e61bd494942025-08-20T02:20:05ZengWileyJournal of Immunology Research2314-88612314-71562018-01-01201810.1155/2018/38610793861079CD4hiCD8low Double-Positive T Cells Are Associated with Graft Rejection in a Nonhuman Primate Model of Islet TransplantationYun Jung Choi0Hi-Jung Park1Hye Jin Park2Kyeong Cheon Jung3Jae-Il Lee4Graduate Course of Translational Medicine, Seoul National University College of Medicine, Seoul 03080, Republic of KoreaGraduate Course of Translational Medicine, Seoul National University College of Medicine, Seoul 03080, Republic of KoreaTransplantation Research Institute, Seoul National University Medical Research Center, Seoul 03080, Republic of KoreaGraduate Course of Translational Medicine, Seoul National University College of Medicine, Seoul 03080, Republic of KoreaGraduate Course of Translational Medicine, Seoul National University College of Medicine, Seoul 03080, Republic of KoreaPeripheral CD4/CD8 double-positive (DP) T cells are associated with autoimmune disorders, cancer, and viral infection. However, the relationship between organ transplantation and DP T cells is unclear. Here, we examined the functional characteristics of peripheral DP T cells and analyzed their significance with respect to islet graft rejection in a nonhuman primate model of islet transplantation. DP T cells were functionally equivalent to conventional CD4 and CD8 T cells in terms of helper and cytotoxic activity, respectively. DP T cells expressed high levels of CXCR5 and PD-1 and secreted IFN-γ, IL-4, and IL-21 in amounts equivalent to those secreted by CD4 or CD8 T cells; also, they produced large amounts of granzyme B and perforin. In addition, under steady-state conditions, DP T cells expressed eomesodermin (Eomes) and promyelocytic leukemia zinc finger (PLZF) proteins, both of which act as transcription factors in innate/memory-like T cells. The number of peripheral DP T cells in the islet transplantation model was high in the group that experienced graft rejection; this was not the case in the long-term survival group. Interestingly, numbers of effector memory T cells (TEM) within the DP T cell population increased significantly during islet graft rejection, as did those of TEM within the cytotoxic CD8 T cells. Furthermore, the most conspicuous of which was the increase of CD4hiCD8low T cell subpopulation at that point. Taken together, the data suggest that peripheral DP T cells showing an innate/memory-like phenotype have both helper and cytotoxic activity in vitro and that they may act as a novel biomarker for graft rejection after islet transplantation.http://dx.doi.org/10.1155/2018/3861079 |
| spellingShingle | Yun Jung Choi Hi-Jung Park Hye Jin Park Kyeong Cheon Jung Jae-Il Lee CD4hiCD8low Double-Positive T Cells Are Associated with Graft Rejection in a Nonhuman Primate Model of Islet Transplantation Journal of Immunology Research |
| title | CD4hiCD8low Double-Positive T Cells Are Associated with Graft Rejection in a Nonhuman Primate Model of Islet Transplantation |
| title_full | CD4hiCD8low Double-Positive T Cells Are Associated with Graft Rejection in a Nonhuman Primate Model of Islet Transplantation |
| title_fullStr | CD4hiCD8low Double-Positive T Cells Are Associated with Graft Rejection in a Nonhuman Primate Model of Islet Transplantation |
| title_full_unstemmed | CD4hiCD8low Double-Positive T Cells Are Associated with Graft Rejection in a Nonhuman Primate Model of Islet Transplantation |
| title_short | CD4hiCD8low Double-Positive T Cells Are Associated with Graft Rejection in a Nonhuman Primate Model of Islet Transplantation |
| title_sort | cd4hicd8low double positive t cells are associated with graft rejection in a nonhuman primate model of islet transplantation |
| url | http://dx.doi.org/10.1155/2018/3861079 |
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