CD52‐negative T cells predict acute graft‐versus‐host disease after an alemtuzumab‐based conditioning regimen

Abstract

Allogeneic haematopoietic stem cell transplantation (HSCT) after a reduced-intensity conditioning (RIC) regimen with fludarabine, melphalan and alemtuzmab is an effective therapy for haematological malignancies. Alemtuzumab, a monoclonal antibody against CD52, a glycosylphosphatidylinositol-anchor-bound surface protein on lymphocytes, depletes T cells to prevent graft-versus-host disease (GVHD). Despite this, acute and chronic GVHD (a/cGVHD) remain life-threatening complications after HSCT. The aim of the present study was to identify parameters to predict GVHD. In 69 patients after HSCT, T-cell subsets were functionally analysed. Reconstitution of CD52 neg T cells and CD52 neg regulatory T cells (Tregs) correlated with onset, severity and clinical course of aGVHD. Patients with aGVHD showed significantly lower levels of CD52 pos T cells compared to patients with cGVHD or without GVHD (P < 0Á001). Analysis of T-cell reconstitution revealed a percentage of <40% of CD52 pos CD4 pos T cells or CD52 pos Tregs at day +50 as a risk factor for the development of aGVHD. In contrast, CD52 neg Tregs showed significant decreased levels of glycoprotein A repetitions predominant (GARP; P < 0Á001), glucocorticoidinduced TNFR-related protein (GITR; P < 0Á001), chemokine receptor (CXCR3; P = 0Á023), CC chemokine receptor type 5 (CCR5; P = 0Á004), but increased levels of immunoglobulin-like transcript 3 (ILT3; P = 0Á001), as well as a reduced suppressive capacity. We conclude that reconstitution of CD52 neg T cells and CD52 neg Tregs is a risk factor for development of aGVHD.

Cigarette Smoke and Morphine Promote Treg Plasticity to Th17 via Enhancing Trained Immunity

“…We screened the expression changes of 373 CDs identified [ 15 ] in three groups of Tregs. As shown in Figure 4 A,B, SM + M specifically upregulate 14 CDs in Tregs including immune checkpoints CD96 and PDCD1 (PD-1) [ 41 ], Treg suppression-promoting CD52 [ 78 ], and resting cluster 6 Treg marker SELL [ 14 ]. SM specifically upregulate the transcript of one CD, which is plastic Treg-promoting MUC1 [ 79 ].…”