Induction of Regulatory T Cells by Intravenous Immunoglobulin: A Bridge between Adaptive and Innate Immunity

Abstract

Intravenous immunoglobulin (IVIg) is a polyclonal immunoglobulin G preparation with potent immunomodulatory properties. The mode of action of IVIg has been investigated in multiple disease states, with various mechanisms described to account for its benefits. Recent data indicate that IVIg increases both the number and the suppressive capacity of regulatory T cells, a subpopulation of T cells that are essential for immune homeostasis. IVIg alters dendritic cell function, cytokine and chemokine networks, and T lymphocytes, leading to development of regulatory T cells. The ability of IVIg to influence Treg induction has been shown both in animal models and in human diseases. In this review, we discuss data on the potential mechanisms contributing to the interaction between IVIg and the regulatory T-cell compartment.

Keywords: autoimmunity; cytokine; dendritic cell; immune modulation; intravenous immunoglobulin; regulatory T cell.

Figure 1

IVIg tolerizes DC, which interacts with T cells to induce Treg. Sialylated IVIg ligates C-type lectin receptors on DC (A), which induces FcγRIIB expression (B) and reduces costimulatory molecule expression (C) and proinflammatory cytokine secretion (D). Anti-inflammatory cytokine and mediator production (E) and presentation of IgG regulatory epitopes (F) decrease proinflammatory cytokine production in naive effector T cells (G) and generate Treg from non-Treg precursors (H). These Treg inhibit effector Th1, Th2, and Th17 cell proliferation and activity (I) in the inflammatory microenvironment and secrete anti-inflammatory cytokines (E) that tolerize DC. CLRs, C-type lectin receptors; GITR, glucocorticoid-induced TNFR family related gene; ITIM, immunoreceptor tyrosine-based inhibition motif; RA, retinoic acid.