Regulation of helper T cell responses to staphylococcal superantigens

S.B. Cameron, M.C. Nawijn, H.F.J. Savelkoul, A.W. Chow

Research output: Contribution to journalArticleAcademicpeer-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 (MHC) class II molecules of antigen-presenting cells outside the peptide groove, and induce massive proliferation of T cells bearing specific Vβ determinants. This tri-molecular interaction leads to uncontrolled release of various proinflammatory cytokines especially interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α), 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 staphylococcal 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 anti-inflammatory 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.
JournalEuropean Cytokine Network
Volume12
Publication statusPublished - 2001

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