NK Cells from RAG- or DCLRE1C-Deficient Patients Inhibit HCMV
The recombination-activating genes (RAGs) and the DNA cross-link repair 1C gene (DCLRE1C) encode the enzymes RAG1, RAG2 and Artemis. They are critical components of the V(D)J recombination machinery. V(D)J recombination is well known as a prerequisite for the development and antigen diversity of T a...
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MDPI AG
2019-11-01
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| Series: | Microorganisms |
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| Online Access: | https://www.mdpi.com/2076-2607/7/11/546 |
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| author | Zeguang Wu Narmadha Subramanian Eva-Maria Jacobsen Kerstin Laib Sampaio Johannes van der Merwe Manfred Hönig Thomas Mertens |
| author_facet | Zeguang Wu Narmadha Subramanian Eva-Maria Jacobsen Kerstin Laib Sampaio Johannes van der Merwe Manfred Hönig Thomas Mertens |
| author_sort | Zeguang Wu |
| collection | DOAJ |
| description | The recombination-activating genes (RAGs) and the DNA cross-link repair 1C gene (DCLRE1C) encode the enzymes RAG1, RAG2 and Artemis. They are critical components of the V(D)J recombination machinery. V(D)J recombination is well known as a prerequisite for the development and antigen diversity of T and B cells. New findings suggested that RAG deficiency impacts the cellular fitness and function of murine NK cells. It is not known whether NK cells from severe combined immunodeficiency (SCID) patients with defective RAGs or DCLRE1C (RAGs<sup>−</sup>/DCLRE1C<sup>−</sup>-NK) are active against virus infections. Here, we evaluated the anti-HCMV activity of RAGs<sup>−</sup>/DCLRE1C<sup>−</sup>-NK cells. NK cells from six SCID patients were functional in inhibiting HCMV transmission between cells in vitro. We also investigated the expansion of HCMV-induced NK cell subset in the RAG- or DCLRE1C-deficient patients. A dynamic expansion of NKG2C<sup>+</sup> NK cells in one RAG-2-deficient patient was observed post HCMV acute infection. Our study firstly reveals the antiviral activity of human RAGs<sup>−</sup>/ DCLRE1C<sup>−</sup>-NK cells. |
| first_indexed | 2024-12-20T01:18:58Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2076-2607 |
| language | English |
| last_indexed | 2024-12-20T01:18:58Z |
| publishDate | 2019-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Microorganisms |
| spelling | doaj.art-8d897f806eb642d287d4e783a28612e12022-12-21T19:58:30ZengMDPI AGMicroorganisms2076-26072019-11-0171154610.3390/microorganisms7110546microorganisms7110546NK Cells from RAG- or DCLRE1C-Deficient Patients Inhibit HCMVZeguang Wu0Narmadha Subramanian1Eva-Maria Jacobsen2Kerstin Laib Sampaio3Johannes van der Merwe4Manfred Hönig5Thomas Mertens6Institute of Virology, Ulm University Medical Center, D-89081 Ulm, GermanyInstitute of Virology, Ulm University Medical Center, D-89081 Ulm, GermanyDepartment of Pediatrics and Adolescent Medicine, Ulm University Medical Center, D-89081 Ulm, GermanyInstitute of Virology, Ulm University Medical Center, D-89081 Ulm, GermanyInstitute of Molecular Virology, Ulm University Medical Center, D-89081 Ulm, GermanyDepartment of Pediatrics and Adolescent Medicine, Ulm University Medical Center, D-89081 Ulm, GermanyInstitute of Virology, Ulm University Medical Center, D-89081 Ulm, GermanyThe recombination-activating genes (RAGs) and the DNA cross-link repair 1C gene (DCLRE1C) encode the enzymes RAG1, RAG2 and Artemis. They are critical components of the V(D)J recombination machinery. V(D)J recombination is well known as a prerequisite for the development and antigen diversity of T and B cells. New findings suggested that RAG deficiency impacts the cellular fitness and function of murine NK cells. It is not known whether NK cells from severe combined immunodeficiency (SCID) patients with defective RAGs or DCLRE1C (RAGs<sup>−</sup>/DCLRE1C<sup>−</sup>-NK) are active against virus infections. Here, we evaluated the anti-HCMV activity of RAGs<sup>−</sup>/DCLRE1C<sup>−</sup>-NK cells. NK cells from six SCID patients were functional in inhibiting HCMV transmission between cells in vitro. We also investigated the expansion of HCMV-induced NK cell subset in the RAG- or DCLRE1C-deficient patients. A dynamic expansion of NKG2C<sup>+</sup> NK cells in one RAG-2-deficient patient was observed post HCMV acute infection. Our study firstly reveals the antiviral activity of human RAGs<sup>−</sup>/ DCLRE1C<sup>−</sup>-NK cells.https://www.mdpi.com/2076-2607/7/11/546human cytomegalovirusnatural killer cellsevere combined immunodeficiency |
| spellingShingle | Zeguang Wu Narmadha Subramanian Eva-Maria Jacobsen Kerstin Laib Sampaio Johannes van der Merwe Manfred Hönig Thomas Mertens NK Cells from RAG- or DCLRE1C-Deficient Patients Inhibit HCMV Microorganisms human cytomegalovirus natural killer cell severe combined immunodeficiency |
| title | NK Cells from RAG- or DCLRE1C-Deficient Patients Inhibit HCMV |
| title_full | NK Cells from RAG- or DCLRE1C-Deficient Patients Inhibit HCMV |
| title_fullStr | NK Cells from RAG- or DCLRE1C-Deficient Patients Inhibit HCMV |
| title_full_unstemmed | NK Cells from RAG- or DCLRE1C-Deficient Patients Inhibit HCMV |
| title_short | NK Cells from RAG- or DCLRE1C-Deficient Patients Inhibit HCMV |
| title_sort | nk cells from rag or dclre1c deficient patients inhibit hcmv |
| topic | human cytomegalovirus natural killer cell severe combined immunodeficiency |
| url | https://www.mdpi.com/2076-2607/7/11/546 |
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