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Keywords:

  • contrasuppression;
  • immunoregulation;
  • suppression

Summary

The original concept of contrasuppression (CS) is evident in many immunoregulatory mechanisms. Inhibition of suppressor activity – CS – may be critical in microbial infection and autoimmunity. The major cellular interactions involved in suppression are the CD25+ FoxP3+ CD4+ T regulatory cells, programmed death-1 (PD-1) : PD-L1/L2 and cytotoxic T lymphocyte antigen-4 (CTLA-4) : CD80/86 pathways. These cellular functions are affected by dendritic cells (DC) and a complex array of cytokines of which interleukin (IL)-2, IL-10, IL-6 and transforming growth factor-β (TGF-β) are especially significant. Inhibition of regulatory cells, suppressor pathways or cytokines, is consistent with CS and can be attributed to IL-6, IL-2, PD-1 or PD-L-1 antibodies, blockade of CTLA-4 : CD80/86 pathway, inhibition of CD40–CD40L pathways, and TGF-β, IL-10 antibodies. Contrasuppression may regulate innate immunity by Toll-like receptor expressed not only in non-cognate DC, monocytes, natural killer cells and γδ T cells but also in adaptive T cells. Furthermore, cross-talk between innate and adaptive immunity may be facilitated by contrasuppressor activity.