CXCR6+ and NKG2C+ Natural Killer Cells Are Distinct With Unique Phenotypic and Functional Attributes Following Bone Marrow Transplantation
Reactivation of human cytomegalovirus (HCMV) is a life-threatening complication in transplant patients. Natural Killer (NK) cells are the first lymphocyte lineage to reconstitute following an allogeneic hematopoietic stem cell transplant (HSCT). Amongst them, NK cell Group 2 isoform C/Killer cell le...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.886835/full |
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| author | Kevin Aviles-Padilla Laura S. Angelo Dwight Fan Dwight Fan Silke Paust Silke Paust Silke Paust |
| author_facet | Kevin Aviles-Padilla Laura S. Angelo Dwight Fan Dwight Fan Silke Paust Silke Paust Silke Paust |
| author_sort | Kevin Aviles-Padilla |
| collection | DOAJ |
| description | Reactivation of human cytomegalovirus (HCMV) is a life-threatening complication in transplant patients. Natural Killer (NK) cells are the first lymphocyte lineage to reconstitute following an allogeneic hematopoietic stem cell transplant (HSCT). Amongst them, NK cell Group 2 isoform C/Killer cell lectin-like receptor subfamily C, member 2 (NKG2C)-expressing NK cells contribute significantly to patient protection upon HCMV reactivation. NKG2C+ NK cells are capable of immunological memory, albeit NK cell memory is not restricted to them. Hepatic C-X-C Motif Chemokine Receptor 6 (CXCR6)-expressing NK cells also mediate memory responses in mice and humans. Small numbers of them circulate and can thus be studied in peripheral blood samples. We hypothesize that NKG2C+ and CXCR6+ NK cell subsets are distinct. To test our hypothesis, we used multi-parametric flow cytometry to determine the phenotypes and effector functions of CD56bright vs. CD56dim and NKG2C+ vs. CXCR6+ human NK cell subsets in the peripheral blood (PB) of pediatric transplant recipients monthly while monitoring patients for HCMV reactivation. Interestingly, we did not find any NKG2C+CXCR6+ NK cells in the transplant recipients’ peripheral blood, suggesting that NKG2C+ and CXCR6+ NK cells are distinct. Also, NKG2C–CXCR6– NK cells, rather than NKG2C+ NK cells, made up most NK cells post-transplant, even in transplant recipients with HCMV viremia. In contrast to NKG2C+ NK cells, CXCR6+ NK cells appeared phenotypically less differentiated but were highly proliferative and produced IFN-γ and TNFα. Our findings contribute to our understanding of post-transplant NK cell development and its implications for human health. |
| first_indexed | 2024-12-12T07:25:54Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-12T07:25:54Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-3de32f28629949259f8f59530588c2922022-12-22T00:33:10ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-06-011310.3389/fimmu.2022.886835886835CXCR6+ and NKG2C+ Natural Killer Cells Are Distinct With Unique Phenotypic and Functional Attributes Following Bone Marrow TransplantationKevin Aviles-Padilla0Laura S. Angelo1Dwight Fan2Dwight Fan3Silke Paust4Silke Paust5Silke Paust6Center for Human Immunobiology, Department of Pediatrics, Texas Children’s Hospital, Houston, TX, United StatesCenter for Human Immunobiology, Department of Pediatrics, Texas Children’s Hospital, Houston, TX, United StatesCenter for Human Immunobiology, Department of Pediatrics, Texas Children’s Hospital, Houston, TX, United StatesThe Developing Investigative Scholar’s Program (DISP), Center for Human Immunobiology, Department of Pediatrics, Texas Children’s Hospital and Rice University, Houston, TX, United StatesCenter for Human Immunobiology, Department of Pediatrics, Texas Children’s Hospital, Houston, TX, United StatesThe Developing Investigative Scholar’s Program (DISP), Center for Human Immunobiology, Department of Pediatrics, Texas Children’s Hospital and Rice University, Houston, TX, United StatesDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, United StatesReactivation of human cytomegalovirus (HCMV) is a life-threatening complication in transplant patients. Natural Killer (NK) cells are the first lymphocyte lineage to reconstitute following an allogeneic hematopoietic stem cell transplant (HSCT). Amongst them, NK cell Group 2 isoform C/Killer cell lectin-like receptor subfamily C, member 2 (NKG2C)-expressing NK cells contribute significantly to patient protection upon HCMV reactivation. NKG2C+ NK cells are capable of immunological memory, albeit NK cell memory is not restricted to them. Hepatic C-X-C Motif Chemokine Receptor 6 (CXCR6)-expressing NK cells also mediate memory responses in mice and humans. Small numbers of them circulate and can thus be studied in peripheral blood samples. We hypothesize that NKG2C+ and CXCR6+ NK cell subsets are distinct. To test our hypothesis, we used multi-parametric flow cytometry to determine the phenotypes and effector functions of CD56bright vs. CD56dim and NKG2C+ vs. CXCR6+ human NK cell subsets in the peripheral blood (PB) of pediatric transplant recipients monthly while monitoring patients for HCMV reactivation. Interestingly, we did not find any NKG2C+CXCR6+ NK cells in the transplant recipients’ peripheral blood, suggesting that NKG2C+ and CXCR6+ NK cells are distinct. Also, NKG2C–CXCR6– NK cells, rather than NKG2C+ NK cells, made up most NK cells post-transplant, even in transplant recipients with HCMV viremia. In contrast to NKG2C+ NK cells, CXCR6+ NK cells appeared phenotypically less differentiated but were highly proliferative and produced IFN-γ and TNFα. Our findings contribute to our understanding of post-transplant NK cell development and its implications for human health.https://www.frontiersin.org/articles/10.3389/fimmu.2022.886835/fullnatural killer cellhuman cytomegalovirusCXCR6NKG2Cbone marrow transplantationhematopoietic stem cell transplantation |
| spellingShingle | Kevin Aviles-Padilla Laura S. Angelo Dwight Fan Dwight Fan Silke Paust Silke Paust Silke Paust CXCR6+ and NKG2C+ Natural Killer Cells Are Distinct With Unique Phenotypic and Functional Attributes Following Bone Marrow Transplantation Frontiers in Immunology natural killer cell human cytomegalovirus CXCR6 NKG2C bone marrow transplantation hematopoietic stem cell transplantation |
| title | CXCR6+ and NKG2C+ Natural Killer Cells Are Distinct With Unique Phenotypic and Functional Attributes Following Bone Marrow Transplantation |
| title_full | CXCR6+ and NKG2C+ Natural Killer Cells Are Distinct With Unique Phenotypic and Functional Attributes Following Bone Marrow Transplantation |
| title_fullStr | CXCR6+ and NKG2C+ Natural Killer Cells Are Distinct With Unique Phenotypic and Functional Attributes Following Bone Marrow Transplantation |
| title_full_unstemmed | CXCR6+ and NKG2C+ Natural Killer Cells Are Distinct With Unique Phenotypic and Functional Attributes Following Bone Marrow Transplantation |
| title_short | CXCR6+ and NKG2C+ Natural Killer Cells Are Distinct With Unique Phenotypic and Functional Attributes Following Bone Marrow Transplantation |
| title_sort | cxcr6 and nkg2c natural killer cells are distinct with unique phenotypic and functional attributes following bone marrow transplantation |
| topic | natural killer cell human cytomegalovirus CXCR6 NKG2C bone marrow transplantation hematopoietic stem cell transplantation |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.886835/full |
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