Regulation of helper T cell responses to staphylococcal superantigens

SB Cameron, MC Nawijn, WWS Kum, HFJ Savelkoul, AW Chow*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

29 Citations (Scopus)

Abstract

Staphylococcal superantigens (sAgs) including toxic shock syndrome toxin-1 (TSST-1) and related enterotoxins are exoproteins with unique immunobiological properties, They bind to major histocompatibility complex (MH-IC) class II molecules of antigen-presenting cells outside the peptide groove, and induce massive proliferation of T cells bearing specific V beta determinants. This tri-molecular interaction leads to uncontrolled release of various proinflammatory cytokines especially interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha), the key cytokines causing sAg-mediated shock, The effector T cells involved in this hyper-immune response are predominantly of the T helper-1 (Th1) phenotype, There is also some evidence that polarization to a Th2 response with the production of classical anti-inflammatory cytokines (such as interleukins IL-4 and IL-6) also occurs. Moreover, the emergence of a novel regulatory T cell (Tr1) subset, producing mainly IL-10 but little or no IL-2 and IL-4, has recently been described following repeated sAg stimulation.

In this review, the current knowledge regarding the regulation of T helper cell subsets in response to staphylacoccal sAgs is critically evaluated, and the role of various cytokines which directly influence T cell differentiation and polarization is summarized, Particular emphasis is directed towards pro-inflammatory as well as antiinflammatory and regulatory effector functions during toxic shock. Based on this-review, we propose that a delayed production of IL-10 by Tr1 cells may be the most prominent driving force in the down-regulation of the Th1 hyper-immune response, and the critical determinant for the eventual recovery of the host.

Original languageEnglish
Pages (from-to)210 - 222
Number of pages13
JournalEuropean cytokine network
Volume12
Issue number2
Publication statusPublished - 2001

Keywords

  • cytokines
  • Th1
  • Th2
  • Tr1
  • IL-10
  • staphylococcal superantigens
  • TOXIC-SHOCK-SYNDROME
  • TUMOR-NECROSIS-FACTOR
  • GROWTH-FACTOR-BETA
  • CYTOKINE GENE-EXPRESSION
  • EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS
  • TOLERANCE IN-VIVO
  • ENTEROTOXIN-B
  • LETHAL SHOCK
  • INTERFERON-GAMMA
  • IMMUNE-RESPONSES

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