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J Immunol. 2017 Jul 1;199(1):159-171. doi: 10.4049/jimmunol.1700214. Epub 2017 Jun 2.

Monoclonal Invariant NKT (iNKT) Cell Mice Reveal a Role for Both Tissue of Origin and the TCR in Development of iNKT Functional Subsets.

Author information

1
Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02215.
2
Whitehead Institute for Biomedical Research, Cambridge, MA 02242; and.
3
Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Boston, MA 02215.
4
Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02215; Stephanie_dougan@dfci.harvard.edu.

Abstract

Invariant NKT (iNKT) cell functional subsets are defined by key transcription factors and output of cytokines, such as IL-4, IFN-γ, IL-17, and IL-10. To examine how TCR specificity determines iNKT function, we used somatic cell nuclear transfer to generate three lines of mice cloned from iNKT nuclei. Each line uses the invariant Vα14Jα18 TCRα paired with unique Vβ7 or Vβ8.2 subunits. We examined tissue homing, expression of PLZF, T-bet, and RORγt, and cytokine profiles and found that, although monoclonal iNKT cells differentiated into all functional subsets, the NKT17 lineage was reduced or expanded depending on the TCR expressed. We examined iNKT thymic development in limited-dilution bone marrow chimeras and show that higher TCR avidity correlates with higher PLZF and reduced T-bet expression. iNKT functional subsets showed distinct tissue distribution patterns. Although each individual monoclonal TCR showed an inherent subset distribution preference that was evident across all tissues examined, the iNKT cytokine profile differed more by tissue of origin than by TCR specificity.

PMID:
28576977
PMCID:
PMC5518629
DOI:
10.4049/jimmunol.1700214
[Indexed for MEDLINE]
Free PMC Article

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