Special regulatory T cell review: The resurgence of the concept of contrasuppression in immunoregulation.
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-beta (TGF-beta) 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-beta, IL-10 antibodies. Contrasuppression may regulate innate immunity by Toll-like receptor expressed not only in non-cognate DC, monocytes, natural killer cells and gammadelta T cells but also in adaptive T cells. Furthermore, cross-talk between innate and adaptive immunity may be facilitated by contrasuppressor activity. ''What's in a name? That which we call a rose by any other name would smell as sweet.'' From Romeo and Juliet (II, 47-8) W. Shakespeare.
D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D051017:Apoptosis Regulatory Proteins / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D061026:Programmed Cell Death 1 Receptor; D015398:Signal Transduction / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D051193:Toll-Like Receptors / Q000276:immunology
D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D051193:Toll-Like Receptors