Invariant NKT cell development requires a full complement of functional CD3 ζ immunoreceptor tyrosine-based activation motifs

Amy M. Becker, Jon S. Blevins, Farol L. Tomson, Jennifer L. Eitson, Jennifer J. Medeiros, Felix Yarovinsky, Michael V. Norgard, Nicolai S C Van Oers

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Invariant NKT (iNKT) cells regulate early immune responses to infections, in part because of their rapid release of IFN-γ and IL-4. iNKT cells are proposed to reduce the severity of Lyme disease following Borrelia burgdorferi infection. Unlike conventional T cells, iNKT cells express an invariant αβ TCR that recognizes lipids bound to the MHC class I-like molecule, CD1d. Furthermore, these cells are positively selected following TCR interactions with glycolipid/CD1d complexes expressed on CD4+CD8 + thymocytes. Whereas conventional T cell development can proceed with as few as 4/10 CD3 immunoreceptor tyrosine-based activation motifs (ITAMs), little is known about the ITAM requirements for iNKT cell selection and expansion.We analyzed iNKT cell development in CD3 ζ transgenic lines with various tyrosine-to-phenylalanine substitutions (YF) that eliminated the functions of the first (YF1,2), third (YF5,6), or all three (YF1-6) CD3 ζ ITAMs. iNKT cell numbers were significantly reduced in the thymus, spleen, and liver of all YF mice compared with wild type mice. The reduced numbers of iNKT cells resulted from significant reductions in the expression of the early growth response 2 and promyelocytic leukemia zinc finger transcription factors. In the mice with few to no iNKT cells, there was no difference in the severity of Lyme arthritis compared with wild type controls, following infections with the spirochete B. burgdorferi. These findings indicate that a full complement of functional CD3 ζ ITAMs is required for effective iNKT cell development.

Original languageEnglish (US)
Pages (from-to)6822-6832
Number of pages11
JournalJournal of Immunology
Volume184
Issue number12
DOIs
StatePublished - Jun 15 2010

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Immunoreceptor Tyrosine-Based Activation Motif
Natural Killer T-Cells
Borrelia burgdorferi
Lyme Disease
CD1d Antigen
Spirochaetales Infections
Borrelia Infections
T-Lymphocytes
Glycolipids
Zinc Fingers
Thymocytes
Infection Control
Phenylalanine
Interleukin-4
Thymus Gland
Tyrosine
Leukemia
Transcription Factors
Spleen
Cell Count

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

Cite this

Invariant NKT cell development requires a full complement of functional CD3 ζ immunoreceptor tyrosine-based activation motifs. / Becker, Amy M.; Blevins, Jon S.; Tomson, Farol L.; Eitson, Jennifer L.; Medeiros, Jennifer J.; Yarovinsky, Felix; Norgard, Michael V.; Van Oers, Nicolai S C.

In: Journal of Immunology, Vol. 184, No. 12, 15.06.2010, p. 6822-6832.

Research output: Contribution to journalArticle

Becker, Amy M. ; Blevins, Jon S. ; Tomson, Farol L. ; Eitson, Jennifer L. ; Medeiros, Jennifer J. ; Yarovinsky, Felix ; Norgard, Michael V. ; Van Oers, Nicolai S C. / Invariant NKT cell development requires a full complement of functional CD3 ζ immunoreceptor tyrosine-based activation motifs. In: Journal of Immunology. 2010 ; Vol. 184, No. 12. pp. 6822-6832.
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