CD1d deficiency limits tolerogenic properties of peritoneal macrophages

Abstract

Invariant natural killer T (iNKT) cells are involved in various autoimmune diseases. Although iNKT cells are arthritogenic, transforming growth factor beta (TGF beta)-treated tolerogenic peritoneal macrophages (Tol-pM Phi) from wild-type (WT) mice are more tolerogenic than those from CD1d knock-out iNKT cell-deficient mice in a collagen-induced arthritis (CIA) model. The underlying mechanism by which pM Phi can act as tolerogenic antigen presenting cells (APCs) is currently unclear. To determine cellular mechanisms underlying CD1d-dependent tolerogenicity of pM Phi, in vitro and in vivo characteristics of pM Phi were investigated. Unlike dendritic cells or splenic M Phi, pM Phi from CD1d(+/-) mice showed lower expression levels of costimulatory molecule CD86 and produced lower amounts of inflammatory cytokines upon lipopolysaccharide (LPS) stimulation compared to pM Phi from CD1d-deficient mice. In a CIA model of CD1d-deficient mice, adoptively transferred pM Phi from WT mice reduced the severity of arthritis. However, pM Phi from CD1d-deficient mice were unable to reduce the severity of arthritis. Hence, the tolerogenicity of pM Phi is a cell-intrinsic property that is probably conferred by iNKT cells during pM Phi development rather than by interactions of pM Phi with iNKT cells during antigen presentation to cognate T cells.