Co-inhibitory profile and cytotoxicity of CD57+PD-1− T cells in end-stage renal disease patients

• DOI: 10.1111/cei.13070
• Publication Date: 2017-10-13T11:32:55Z
• Authors: R Kraaijeveld; G N de Graav; M Dieterich; N H R Litjens; D A Hesselink; C C Baan
• Keywords: Adult; Cytotoxicity, Immunologic; Graft Rejection; Male; 0301 basic medicine; Isoantigens; EMC MM-04-39-05; Programmed Cell Death 1 Receptor; Middle Aged; Kidney Transplantation; 3. Good health; Abatacept; 03 medical and health sciences; CD57 Antigens; Antigens, CD; Signaling Lymphocytic Activation Molecule Family; Humans; Kidney Failure, Chronic; Female; Cells, Cultured; Immunosuppressive Agents; Aged; Cell Proliferation; Netherlands

SummaryBlockade of the CD80/86-CD28 pathway by belatacept after kidney transplantation is associated with an increased risk of rejection compared with standard, calcineurin inhibitor (CNI)-based therapy. CD28− T cells, which express CD57, are not susceptible to belatacept treatment. High numbers of CD4+CD57+programmed death 1 (PD-1)− T cells pretransplantation have been associated with a higher chance of rejection, although conflicting data have been reported. To investigate the working mechanism behind this possible higher chance of rejection, we studied the expression of co-inhibitory molecules (CD223, CD244 and PD-1), proliferative capacity and cytotoxic potential of fluorescence activated cell sorted (FACS) CD4+CD57+PD-1− and CD8+CD57+PD-1− T cells, and their CD57− control populations, after alloantigen stimulation. The effect of belatacept on the cytotoxic capacity of pretransplantation peripheral blood mononuclear cells from 20 patients who received belatacept post-transplantation was also tested. Expression of co-inhibitory molecule CD223 increased by approximately 10-fold after allogeneic stimulation in all four T cell subsets. Proliferation and up-regulation of CD244 and PD-1 was observed for CD4+CD57−PD-1− T cells after allogeneic stimulation, but no up-regulation of these markers occurred on CD8+ T cells or CD4+CD57+PD-1− T cells. However, CD4+CD57+PD-1− T cells and, to a lesser extent, CD8+CD57+PD-1− T cells displayed higher cytotoxicity as indicated by granzyme B expression. Belatacept inhibited the cytotoxic potential of CD4+CD57+PD-1− T cells (median of inhibition 31%, P < 0·01) and CD8+CD57+PD-1− T cells (median of inhibition 10%, P < 0·05). In conclusion, alloantigen-activated CD4+CD57+PD-1− T cells exhibited a less proliferative but more cytotoxic profile than their CD57− counterparts. Their cytotoxic capacity can be inhibited partly by belatacept and was not associated with development of rejection after kidney transplantation.