Cutting edge: B and T lymphocyte attenuator signaling on NKT cells inhibits cytokine release and tissue injury in early immune responses

Mendy L. Miller, Yonglian Sun, Yang Xin Fu

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

The role of coinhibition in an immune response is thought to be critical for the contraction of an adaptive immune response in its waning phases. We present evidence that B and T lymphocyte attenuator (BTLA) coinhibitory signaling is required to temper early inflammation. Using an in vivo Con A challenge model of acute hepatitis, we observed reduced survival and increased early serum cytokine secretion in BTLA-/- mice as compared with wild-type mice. In vitro, liver mononuclear cells from BTLA-/- mice are hyperresponsive to anti-CD3, Con A, and α-galactosylceramide stimulation and secrete higher levels of TNF-α, IFN-γ, IL-2, and IL-4. We found this was in part due to negative regulation of NKT cells by BTLA, as early cytokine inhibition from whole liver mononuclear cells or purified NKT cells depends upon BTLA signaling. Overall, our data demonstrate that coinhibition is active in early immune responses through BTLA regulation of NKT cells.

Original languageEnglish (US)
Pages (from-to)32-36
Number of pages5
JournalJournal of Immunology
Volume183
Issue number1
DOIs
StatePublished - Jul 1 2009

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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