Mechanisms of interleukin-10-mediated immune suppression.
Specific immune suppression and induction of anergy are essential processes in the regulation and circumvention of immune defence. Interleukin-10 (IL-10), a suppressor cytokine of T-cell proliferative and cytokine responses, plays a key regulatory role in tolerizing exogenous antigens during specific immunotherapy (SIT) of allergy and natural exposure to antigens. Specific T-cell tolerance is directed against the T-cell epitopes of an antigen and characterized by suppressed proliferative and T helper type 1 (Th1) and type 2 (Th2) cytokine responses. IL-10 elicits tolerance in T cells by selective inhibition of the CD28 co-stimulatory pathway and thereby controls suppression and development of antigen-specific immunity. IL-10 only inhibits T cells stimulated by low numbers of triggered T-cell receptors and which therefore depend on CD28 co-stimulation. T cells receiving a strong signal from the T-cell receptor alone, and thus not requiring CD28 co-stimulation, are not affected by IL-10. IL-10 inhibits CD28 tyrosine phosphorylation, the initial step of the CD28 signalling pathway, and consequently the phosphatidylinositol 3-kinase p85 binding to CD28. Together these results demonstrate that IL-10-induced selective inhibition of the CD28 co-stimulatory pathway acts as a decisive mechanism in determining whether a T cell will contribute to an immune response or become anergic.
Akdis
C A
CA
Swiss Institute of Allergy and Asthma Research (SIAF), Davos, Switzerland. akidsac@siaf.unizh.ch
Blaser
K
K
D016207:Cytokines / Q000276:immunology; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology; D007108:Immune Tolerance / Q000276:immunology*; D007073:Immunoglobulin E / Q000096:biosynthesis; D016753:Interleukin-10 / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology
D016207:Cytokines; D016753:Interleukin-10; D007073:Immunoglobulin E