Article ; Online: Natural killer cell immunosuppressive function requires CXCR3-dependent redistribution within lymphoid tissues.
The Journal of clinical investigation
2021 Volume 131, Issue 18
Abstract: NK cell suppression of T cells is a key determinant of viral pathogenesis and vaccine efficacy. This process involves perforin-dependent elimination of activated CD4+ T cells during the first 3 days of infection. Although this mechanism requires cell- ... ...
| Abstract | NK cell suppression of T cells is a key determinant of viral pathogenesis and vaccine efficacy. This process involves perforin-dependent elimination of activated CD4+ T cells during the first 3 days of infection. Although this mechanism requires cell-cell contact, NK cells and T cells typically reside in different compartments of lymphoid tissues at steady state. Here, we showed that NK cell suppression of T cells is associated with transient accumulation of NK cells within T cell-rich sites of the spleen during lymphocytic choriomeningitis virus infection. The chemokine receptor CXCR3 was required for this relocation and suppression of antiviral T cells. Accordingly, NK cell migration was mediated by type I IFN-dependent promotion of CXCR3 ligand expression. In contrast, adenoviral vectors that weakly induced type I IFN and did not stimulate NK cell inhibition of T cells also did not promote measurable redistribution of NK cells to T cell zones. Exogenous IFN rescued NK cell migration during adenoviral vector immunization. Thus, type I IFN and CXCR3 were critical for properly positioning NK cells to constrain antiviral T cell responses. Development of strategies to curtail migration of NK cells between lymphoid compartments may enhance vaccine-elicited immune responses. |
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| MeSH term(s) | Animals ; Cell Movement/immunology ; Host Microbial Interactions/immunology ; Immune Tolerance ; Immunity, Innate ; Killer Cells, Natural/immunology ; Lymphocyte Activation ; Lymphocytic Choriomeningitis/immunology ; Lymphocytic Choriomeningitis/virology ; Lymphocytic choriomeningitis virus/immunology ; Lymphoid Tissue/immunology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Receptors, CXCR3/metabolism ; T-Lymphocytes/immunology |
| Chemical Substances | Cxcr3 protein, mouse ; Receptors, CXCR3 |
| Language | English |
| Publishing date | 2021-07-27 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 3067-3 |
| ISSN | 1558-8238 ; 0021-9738 |
| ISSN (online) | 1558-8238 |
| ISSN | 0021-9738 |
| DOI | 10.1172/JCI146686 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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