The impact of belatacept on the phenotypic heterogeneity of renal T cell–mediated alloimmune response: The critical role of maintenance treatment and inflammatory load

Abstract

The introduction of calcineurin inhibitors (CNIs) ushered a new era of renal transplantation by dramatically improving short-term allograft survival. 1,2 However, CNIs also became an additional contributor to late allograft loss due to their deleterious toxicity profile. 3 Since the late 1990s, there have been ongoing efforts to minimize CNI use or replace them with less toxic agents such as mycophenolate mofetil (MMF) with or without mechanistic target of rapamycin (mTOR) inhibitors and steroid. 4,5 The most recent and, so far, most promising attempt was the introduction of belatacept 6 (a second-generation CTLA4-Ig). Belatacept acts by blocking the

Multiple Shades of Gray—Macrophages in Acute Allograft Rejection

“…There is an obvious link between belatacept and macrophages as this compound blocks CD80/86 co-stimulatory molecules on APCs, which also include macrophages [163]. A study of renal transplant biopsies from patients treated with either calcineurin inhibitor or belatacept indicated that co-stimulatory blockade with belatacept was positively associated with genes related to innate immune responses including receptors of phagocytes (e.g., CD16, CD14, CD68, CD209, and TLR4) [144]. However, the effect of belatacept on macrophages is not well investigated.…”