Abstract
gamma delta TCR+ hybridoma cells prepared from mesenteric lymph node cells of animals receiving donor-specific immunization via the portal vein can adoptively transfer this increased graft survival to naive animals. Analysis of TCR gamma-chain junctional sequence diversity suggested that some 40 to 50% of the hybridomas expressed gamma-chain junctional sequence diversity and were stimulated to produce cytokines both by heat shock proteins and by minor histocompatibility Ag-specific irradiated peritoneal cells. The remaining gamma delta TCR+ hybridoma cells expressed TCR with a common gamma-chain junctional sequence and were stimulated to cytokine production by MHC-matched, but minor histocompatibility Ag-mismatched (as well as matched), peritoneal cells, but not by heat shock proteins. We have compared the effectiveness of representative hybridomas expressing unique gamma-chain junctional sequences or common gamma-chain junctional sequences for prolongation of donor-specific or third-party (MHC-matched or MHC-mismatched) skin grafts. Our data show a good correlation between the specificity for stimulation for cytokine production in vitro and efficacy in graft prolongation assays in vivo. Hybridoma cells expressing unique gamma-chain junctional sequences that showed Ag-specific stimulation of cytokine production in vitro and skin graft survival in vivo augmented survival of third-party skin grafts if simultaneously transplanted with both Ag-specific and third-party skin grafts. Graft prolongation in vivo using cells from either population of gamma delta TCR+ hybridomas was decreased by infusion of anti-IL-10 mAb and abolished when both anti-IL-10 and anti-TGF-beta Abs were used together.
