Staphylococcal enterotoxin B-induced activation and concomitant resistance to cell death in CD28-deficient HLA-DQ8 transgenic mice

Govindarajan Rajagopalan, Michele K. Smart, Eric V. Marietta, Chella S. David

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

HLA class II molecules present superantigens more efficiently than their murine counterpart. Therefore, transgenic mice expressing HLA-DQ8 with and without CD28 were used to address the role of CD28 in staphylococcal enterotoxin B (SEB)-driven immune responses. SEB-induced in vitro proliferation of naive DQ8.CD28-/- splenocytes was comparable to DQ8.CD28+/+ cells, and was several fold higher than that of C57BL/10 and BALB/c splenocytes. SEB-activated, naive DQ8.CD28-/- cells in vitro produced significantly less IL-2, IL-4 and IL-10 than DQ8.CD28+/+ cells, while IFN-γ and IL-6 production was comparable. SEB-induced in vivo expansion of CD4+ T cells and, to a greater extent, CD8+ T cells was compromised in DQ8.CD28-/- mice, indicating that SEB-induced proliferation of CD8+ T cells is more dependent on CD28 co-stimulation. Upon re-stimulation, SEB-primed CD28+/+ T cells failed to proliferation, but were capable of producing cytokines. Conversely, CD28-/- T cells were capable of proliferation, but not cytokine production. SEB-primed CD28-deficient cells produced significantly less nitric oxide when compared to CD28-sufficient cells following re-stimulation with SEB. CD28+/+ and not CD28-/- mice were highly susceptible to SEB-induced lethal shock characterized by significantly elevated serum IFN-γ. Thus, (i) efficient presentation of SEB by HLA-DQ8 circumvents co-stimulation through CD28, (ii) unique CD28-derived signals are mandatory for generation of certain effector functions, and (iii) absence of CD28-derived signals confers resistance to activation-induced cell death and protects mice from SEB-induced shock.

Original languageEnglish (US)
Pages (from-to)801-812
Number of pages12
JournalInternational Immunology
Volume14
Issue number7
DOIs
StatePublished - Jan 1 2002

Keywords

  • Co-stimulatory molecule
  • MHC
  • Rodent
  • Superantigen
  • Transgenic/knockout

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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