Abatacept Promotes Regulatory B Cell Functions, Enhancing Their Ability to Reduce the Th1 Response in Rheumatoid Arthritis Patients through the Production of IL-10 and TGF-β

Abstract

Abatacept mimics natural CD152 and competes with CD28 for binding to CD80/CD86 on APC, such as B cells, thereby preventing T cell activation. However, its potential impact on B cells has not been identified. The aim of this study was to assess whether abatacept can potentiate the immunoregulatory properties of B cells in vitro and in patients with rheumatoid arthritis (RA). T and B cells from healthy controls were purified. The suppressor properties of B cells in the presence of abatacept or control IgG1 were evaluated based on the ability of these cells to inhibit the polyclonal expansion (anti-CD3/CD28 stimulation) of T cells or their differentiation into Th1 or Th17 cells. Similar analyses were also performed with cells from RA patients before and 3 mo after abatacept initiation. Abatacept significantly potentiated regulatory B cell regulatory functions by enhancing their ability to produce IL-10 and TGF-β, resulting in the increased generation of regulatory T cells and limited T cell proliferation and differentiation into Th1 and Th17 cells. Interestingly, B cells isolated from patients that received a 3-mo treatment with abatacept had an increased ability to reduce T cell functions, confirming the above observations. Abatacept binding to CD80/CD86 induces and promotes regulatory B cell functions by enhancing the ability of these cells to produce IL-10 and TGF-β in vitro and in RA patients.

Long-term effects of abatacept on atherosclerosis and arthritis in older vs. younger patients with rheumatoid arthritis: 3-year results of a prospective, multicenter, observational study

“…In the atherosclerotic plaque, T cells produce various cytokines that may further contribute to plaque formation [ 33 ]. As ABT has been shown to inhibit T-cell activation, it could potentially reduce plaque scores [ 34 ]. Reportedly, plaques in unstable angina patients present clonally expanded peripheral blood CD4 T cells lacking CD28 expression (CD4 + CD28 null ) [ 35 ], which are also increased in patients with RA [ 36 ].…”

Dose-dependent effects of oleuropein administration on regulatory T-cells in patients with rheumatoid arthritis: An in vitro approach

“… 13 , 14 , 53 However, the flow cytometry results showed no statistically significant difference in Treg frequencies between HC and RA patients, which might be related to the different effects of conventional and biological DMARDs on Tregs in RA patients. 54 – 57 A number of studies have shown that treatment of RA patients with some but not all of DMARDs, such as methotrexate, tumor necrosis factor-α inhibitors (TNF-αi), adalimumab, and etanercept can restore the regulatory functions of Tregs and increase the frequency of these cells through various mechanisms. 54 , 55 , 58 , 59 Therefore, the effects of OLEU on Tregs could be influenced by treatment of RA patients with various DMARDs.…”

Biologic Mechanisms of Macrophage Phenotypes Responding to Infection and the Novel Therapies to Moderate Inflammation

“…The downregulation of TGF-β can easily lead to various diseases, including fibrosis, chronic inflammation and malignant tumors [61]. Recent studies have shown that both regulatory T cells (Treg) and B cells (Breg) can produce TGF-β through the endocrine pathway, which can promote the transformation of the macrophages from pro-inflammation into anti-inflammation [62,63].…”