NK Cells from RAG- or DCLRE1C-Deficient Patients Inhibit HCMV

Zeguang Wu; Narmadha Subramanian; Eva-Maria Jacobsen; Kerstin Laib Sampaio; Johannes van der Merwe; Manfred Hönig; Thomas Mertens

doi:10.3390/microorganisms7110546

NK Cells from RAG- or DCLRE1C-Deficient Patients Inhibit HCMV

Microorganisms. 2019 Nov 10;7(11):546. doi: 10.3390/microorganisms7110546.

Authors

Zeguang Wu¹, Narmadha Subramanian¹, Eva-Maria Jacobsen², Kerstin Laib Sampaio¹, Johannes van der Merwe³, Manfred Hönig², Thomas Mertens¹

Affiliations

¹ Institute of Virology, Ulm University Medical Center, D-89081 Ulm, Germany.
² Department of Pediatrics and Adolescent Medicine, Ulm University Medical Center, D-89081 Ulm, Germany.
³ Institute of Molecular Virology, Ulm University Medical Center, D-89081 Ulm, Germany.

Abstract

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^-/DCLRE1C^--NK) are active against virus infections. Here, we evaluated the anti-HCMV activity of RAGs^-/DCLRE1C^--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⁺ NK cells in one RAG-2-deficient patient was observed post HCMV acute infection. Our study firstly reveals the antiviral activity of human RAGs^-/ DCLRE1C^--NK cells.

Keywords: human cytomegalovirus; natural killer cell; severe combined immunodeficiency.