Natural killer cell immunosuppressive function requires CXCR3-dependent redistribution within lymphoid tissues

NK cell suppression of T cells is a key determinant of viral pathogenesis and vaccine efficacy. This process involves perforindependent 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 resid...

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Bibliographic Details
Published inThe Journal of clinical investigation Vol. 131; no. 18; pp. 1 - 7
Main Authors Ali, Ayad, Canaday, Laura M, Feldman, H Alex, Cevik, Hilal, Moran, Michael T, Rajaram, Sanjeeth, Lakes, Nora, Tuazon, Jasmine A, Seelamneni, Harsha, Krishnamurthy, Durga, Blass, Eryn, Barouch, Dan H, Waggoner, Stephen N
Format Journal Article
LanguageEnglish
Published Ann Arbor American Society for Clinical Investigation 01.09.2021
Subjects
Antibodies
Biomedical research
CD4 antigen
Cell adhesion
Cell adhesion & migration
Cell migration
Chemokine receptors
Chemokines
CXCR3 protein
Expression vectors
Hepatitis B
Immunization
Infections
Interferon
Ligands
Localization
Lymphatic system
Lymphocytes
Lymphocytes T
Lymphoid tissue
Natural killer cells
Perforin
Spleen
Vaccine efficacy
Vaccines
Viruses
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Summary:NK cell suppression of T cells is a key determinant of viral pathogenesis and vaccine efficacy. This process involves perforindependent 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.
ISSN:0021-9738
1558-8238
DOI:10.1172/JCI146686.