Blockade 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.

Additional Metadata
Keywords Co-stimulation, Cytotoxicity, T cells, Transplantation
Persistent URL dx.doi.org/10.1111/cei.13070, hdl.handle.net/1765/102872
Journal Clinical and Experimental Immunology
Citation
Kraaijeveld, R, de Graav, G.N, Dieterich, M, Litjens, N.H.R, Hesselink, D.A, & Baan, C.C. (2017). Co-inhibitory profile and cytotoxicity of CD57+PD-1- T cells in end-stage renal disease patients. Clinical and Experimental Immunology. doi:10.1111/cei.13070