Bone marrow cells promote TH2 polarization and inhibit virus-specific CTL generation

This laboratory recently reported chat human bone marrow cells (BMC) inhibi t the generation of virus-specific CTL in culture. The culture supernatants contained increased levels of prostaglandin E-2 (PGE(2)) (shown to favor T H2 cell development) and also inhibited EBV-CTL effector cell development. In this study, we obtained PDL from Epstein-Barr virus (EBV) IgG antibody p ositive kidney transplant recipients (R) and their living-related donors (L RD) one year after renal transplantation. EBV-specific CTL were then genera ted in vitro by stimulating PDL with autologous EBV-transformed B cells (EB V-B) in the presence or absence of autologous BMC. The addition of BMC ro t he EBV-CTL generation cultures increased the intracellular expression in CD 3+ cells of IL-4,-5,-6,-10, and -13. These CD3+ cells also expressed increa sed levels of the TH2 associated receptor CCR3. Inhibition was even observe d by preparing EBV-CTL generating cultures in trans-wells char separated th e autulogous BMC from the PBL + EBV-B. It was then observed that CD3+ cells obtained after 7 days of culture in the presence of autologous BMC could b e used as inhibitors of EBV-CTL generation. Protein Kinase A (PKA), a cAMP kinase chat is involved in the upregulation of TH2 cytokine activity, was i ncreased in EBV-CTL cultures by the presence of BMC. Additionally, IL-4-med iated signal transduction and activation of transcription (STAT-6) phosphor ylation was slightly increased. These results show that the BMC inhibition is mediated by soluble factors (cytokines) and char cell-cell contact in th is autologous system is not required, so that BMC (at least partially, via cytokine production) promote TH2 polarization in culture. Moreover, TH2 cel ls induced by culturing with autologous BMC directly inhibit EBV-CTL genera tion, and TH2 associated PKA, CCR3, and STAT-6 phosphorylation are enhanced by BMC. (C) American Society for Histocompatibility and Immunogenetics, 20 00. Published by Elsevier Science Inc.