Activation Markers on B and T Cells and Immune Checkpoints in Autoimmune Rheumatic Diseases

Abstract

In addition to identifying the major B- and T-cell subpopulations involved in autoimmune rheumatic diseases (ARDs), in recent years special attention has been paid to studying the expression of their activation markers and immune checkpoints (ICPs). The activation markers on B and T cells are a consequence of the immune response, and these molecules are considered as sensitive specific markers of ARD activity and as promising targets for immunotherapy. ICPs regulate the activation of the immune response by preventing the initiation of autoimmune processes, and they modulate it by reducing immune cell-induced organ and tissue damage. The article considers the possible correlation of ICPs with the activity of ARDs, the efficacy of specific ARD treatments, and the prospects for the use of activation molecules and activation/blocking ICPs for the treatment of ARDs.

Keywords: B-cell; T-cell; autoimmune rheumatic diseases; immune checkpoints; targeted immunotherapy.

Figure 1

CD95 stimulation and potential links to inflammation activation. Three molecular complexes can occur with CD95 involvement to induce chronic inflammation (blue circle), apoptosis (pink circle), or necrosis (green circle). Apoptotic and necroptotic complexes control each other and the inflammatory complex (black lines). CD95 (FAS) promotes DC maturation and differentiation of Th17 and induction of the secretion of pro-inflammatory cytokines (IL-1β, TNF-α) and CXC or CC chemokines. The CD95-mediated apoptotic and non-apoptotic signaling pathways share many factors, such as the apoptotic factors FADD and caspase-8. Interaction of CD95 L with CD95 favors the recruitment of FADD to the death domain of CD95. Abbreviations: Th, T helper; DCs, dendritic cells; IL, Interleukin; TNF, Tumoral necrosis factor; CD95L, CD95 Ligand; MMP, Matrix metalloproteinase; PSGL-1, P-selectin glycoprotein ligand-1; FADD, Fas-associated death domain; Casp8, Caspase-8.

Figure 2

Effect of the OX40-OX40L interaction on different T-cell subsets. Abbreviations: Th, T helper; IL, Interleukin; IFN-γ, Interferon gamma; TNF, Tumoral necrosis factor; TGF-β, Transforming growth factor beta; Tregs, T regulatory cells; Tfh, T follicular helper cells; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells.