Cross talk between the bone and immune systems: osteoclasts function as antigen-presenting cells and activate CD4+ and CD8+ T cells

Abstract

The bone and immune systems are closely related through cellular and molecular interactions. Because bone-resorbing osteoclasts (OCs) are derived from the monocyte/macrophage lineage, similar to dendritic cells (DCs), we hypothesized that OCs could serve as antigen-presenting cells (APCs) to activate T cells. In this study, OCs were generated from human monocytes with stimulation by receptor activator of nuclear factor kappaB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). Results showed that, similar to DCs, OCs express major histocompatibility complex (MHC) classes I and II, and CD80, CD86, and CD40; and uptake soluble antigens. OCs secrete interleukin-10 (IL-10), transforming growth factor-beta (TGF-beta), IL-6, and tumor necrosis factor-alpha (TNF-alpha), but not IL-12p70. OCs present allogeneic antigens and activate both CD4+ and CD8+ alloreactive T cells in an MHC-restricted fashion. OCs also present soluble protein tetanus toxoid to activate autologous CD4+ T cells. These findings indicate that OCs can function as APCs and activate both CD4+ and CD8+ T cells. Thus, our study provides new insight into the effect of OCs on the immune system and may help develop novel strategies for treating diseases such as rheumatoid arthritis and multiple myeloma, which affect both the bone and immune systems.

Osteoclasts promote immune suppressive microenvironment in multiple myeloma: therapeutic implication

“…Because OCs can function as APCs, 13 we measured CD80/86 molecules, which are expressed by APCs and involved in T-cell co-stimulation. CD80 expression was significantly induced, whereas CD86 was slightly upregulated in OCs compared with monocytes ( Figure 1C).…”

Osteoimmunology and Its Implications for Transplantation

“…Osteoclasts selectively recruit and activate CD8 T cells (17,18). The osteoclast-recruited CD8 T cells express CD25 and FoxP3, and therefore are defined as osteoclast-induced regulatory CD8 T cells (19).…”

Chemotactic and Immunoregulatory Properties of Bone Cells are Modulated by Endotoxin-Stimulated Lymphocytes

“…Although several recent studies confirmed immunological properties of bone cells [19][20][21][22]24], direct chemotactic and immunomodulatory effects of OBL and OCL have not been precisely determined. In the co-culture model we demonstrated both the ability of lymphocytes to affect bone cell differentiation and their chemotactic properties, and of bone cells to modulate the cytokine and activation profile of lymphoid cells.…”

“…OCL, expressing MHC-I/II and costimulatory molecules, can uptake soluble antigens serving as antigen-presenting cells for alloreactive T lymphocytes [24]. In response to immune cells these bone cells produce cytokines, chemokines, extracellular matrix proteins and other inflammatory mediators [25][26][27].…”