The Variable Genomic NK Cell Receptor Locus Is a Key Determinant of CD4+ T Cell Responses During Viral Infection

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2020 Mar 11

PMID 32153566

Authors

Jana Raynor

Adora Lin

Sarah A Hummel

Kristin Lampe

Michael Jordan

Kasper Hoebe

David A Hildeman

Affiliations

Soon will be listed here.

Abstract

Increasing evidence points to a key role for NK cells in controlling adaptive immune responses. In studies examining the role of CD1d on CD4+ T cell responses, we found that a line of CD1d-deficient mice on the C57BL/6J background had a homozygous 129 locus on chromosome 6 containing the entire NK cell gene cluster. Mice possessing this locus (C57BL/6.NKC) displayed a >10-fold reduction in antigen-specific CD4+ T cell responses after intracranial infection with lymphocytic choriomeningitis virus (LCMV). Neither parental strain displayed defects in viral-specific CD4+ T cell responses. Interestingly, following infection, increased numbers of NK cells accumulated in the lymph nodes of C57BL/6.NKC mice and displayed enhanced functionality. Moreover, depletion of NK cells with anti-asialo-GM-1 antibody in C57BL/6.NKC mice resulted in a >20-fold increase in viral-specific CD4+ T cell responses. Mechanistically, we found that dendritic cell antigen presentation and early type I IFN production were significantly decreased in C57BL/6.NKC mice, but were restored in perforin-deficient C57BL/6.NKC mice or following NK depletion. Together, these data reveal that the variable genomic regions containing the activating/inhibitory NK cell receptors are key determinants of antigen-specific CD4+ T cell responses, controlling type I IFN production and the antigen-presenting capacity of dendritic cells.

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