Bone marrow cells inhibit the generation of autologous EBV-specific CTL

Recently, we reported that human bone marrow cells (BMC) inhibited the prol iferative (recall) response of lymphocytes to Epstein-Barr virus (EBV) and cytomegalovirus (CMV) protein antigens [12]. To clarify further the effect of BMC on the immune response ro viral antigens, we obtained PBL from EBV I gG antibody positive kidney transplant recipients (R) and their living-rela ted donors (LRD) I year after renal transplantation and generated EBV-speci fic CTL in vitro in the presence or absence of autologous BMC. The addition of freshly aspirated autologous iliac crest BMC from either R or LRD cause d a significant inhibitory effect on the generation of EBV-specific CTL fro m CTL precursors, in contrast to the addition of autologous PBL used as con trols (62.29 +/- 10.85% inhibition using BMC from the kidney transplant rec ipients; 74.47 +/- 15.21% inhibition using BMC from the living-related dono rs). This inhibitory effect was only exerted during the CTL generation phas e; but not in the effector CTL killing phase. The expression of CD94, a com ponent of the killer inhibitory receptor (KIR) on CD3(+) cells was elevated in the cultures with BMC, in contrast to the cultures without BMC. The BMC inhibitory effect was partially abrogated by pre-incubation of the CTL eff ectors with anti-CD94 monoclonal antibody, in contrast with its isotype con trol. In addition, supernatants obtained from the CTL generating cultures w ith BMC contained high levels of prostaglandin E-2 (PGE(2)), and EBV-specif ic CTL activity was inhibited by the addition of exogenous PGE(2) in the ab sence of BMC. The induction of CD40L cell surface expression by anti-CD3 wa s also decreased on the effector T cell population when BMC were added. The re was a concomitant reduction in protein kinase C (PKC) activity. These st udies demonstrate that BMC exert an inhibitory effect on T cell-mediated im munity to viral antigens in humans by regulating autologous effector T cell generation and early T cell activation signaling pathways. (C) American So ciety for Histocompatibility and Immunogenetics, 2000. Published by Elsevie r Science Inc.