A subset of gamma delta T-cell receptor-positive cells produce T-helper type-2 cytokines and regulate mouse skin graft rejection following portal venous pretransplant preimmunization.

C3H/HeJ mice received B10.BR skin grafts following portal or lateral tail vein infusion of irradiated B10.BR spleen cells. Thereafter mice were injected with anti-alpha beta or anti-gamma delta T-cell receptor (TCR) monoclonal antibody (mAb). Anti-gamma delta TCR mAb abolished the increased graft survival afforded by portal venous (p.v.) immunization, and reversed the bias towards expression of mRNA for type-2 cytokines [interleukin-4 (IL-4), IL-10] seen in lymphoid tissue of p.v.-immunized mice. When gamma delta TCR+ and alpha beta TCR+ cells were isolated from the intestinal epithelial compartment (IEL), liver or Peyer's Patch (PP) of p.v.-immunized mice, the gamma delta TCR+ cells were found to be enriched in cells producing type-2 cytokines on rechallenge with irradiated B10.BR cells in vitro. gamma delta TCR+ cells from p.v.-immunized mice were further expanded in vitro with anti-CD3 and cytokines (combined IL-2 and IL-4). Following expansion these cells were capable of adoptively transferring increased B10.BR skin graft survival to naive mice, and continued to show a bias in type-2 cytokine synthesis after allostimulation in vitro. When gamma delta TCR chain expression was assessed in cells taken from p.v.-immunized mice, or in cells expanded in culture, our data suggest that p.v. immunization leads to oligoclonal, not polyclonal, expansion of those gamma delta TCR+ cells involved in inhibition of graft rejection.