T Cell–Macrophage Interactions and Granuloma Formation in Vasculitis

Abstract

Granuloma formation, bringing into close proximity highly activated macrophages and T cells, is a typical event in inflammatory blood vessel diseases, and is noted in the name of several of the vasculitides. It is not known whether specific properties of the microenvironment in the blood vessel wall or the immediate surroundings of blood vessels contribute to granuloma formation and, in some cases, generation of multinucleated giant cells. Granulomas provide a specialized niche to optimize macrophage–T cell interactions, strongly activating both cell types. This is mirrored by the intensity of the systemic inflammation encountered in patients with vasculitis, often presenting with malaise, weight loss, fever, and strongly upregulated acute phase responses. As a sophisticated and highly organized structure, granulomas can serve as an ideal site to induce differentiation and maturation of T cells. The granulomas possibly seed aberrant Th1 and Th17 cells into the circulation, which are known to be the main pathogenic cells in vasculitis. Through the induction of memory T cells, aberrant innate immune responses can imprint the host immune system for decades to come and promote chronicity of the disease process. Improved understanding of T cell–macrophage interactions will redefine pathogenic models in the vasculitides and provide new avenues for immunomodulatory therapy.

Proteinase 3-ANCA Vasculitis versus Myeloperoxidase-ANCA Vasculitis

“…Granuloma formation is thought to be initiated by small aggregates of neutrophils surrounding necrotic areas (microabscess). [85][86][87] In GPA, granulomatous inflammation can be found in several affected organs, a feature not found in MPA. 88 Granuloma formation can be found in both PR3-ANCA-positive patients and MPO-ANCA-positive patients diagnosed with GPA.…”

Pro-inflammatory and anti-inflammatory T cells in giant cell arteritis

“…By definition, granulomas are organized lymphoid microstructures, composed of two major cell populations: macrophages, sometimes called histiocytes, which may fuse to form giant cells and CD4 T cells. Granulomas have been implicated in containment of intracellular bacterial infections and difficult-to-digest irritants, but convincing data implicating either in the pathogenesis of GCA are missing (5, 6). …”

Dendritic cells trigger imbalance of Th1/Th2 cells in silica dust exposure rat model via MHC-II, CD80, CD86 and IL-12

“…14,15 Previous studies have demonstrated that CD4 + T cells are considered as the key participant in silicosis, and Th1/Th2 cells participate in the pathogenesis of silicosis. 16,17 DCs are the most efficient APCs that can activate both T cells and B cells and thus, they act as a bridge between innate and adaptive immunity. [18][19][20][21] Besides, DCs also have the ability to inuence T cell polarization via three ways: (i) antigen presentation, (ii) co-stimulatory molecule expression, and (iii) direct contribution by DCs to the immediate cytokine milieu that directs the resultant Th cell response.…”