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.
Gorczynski
R M
RM
Department of Surgery, University of Toronto, Ontario, Canada.
Chen
Z
Z
Hoang
Y
Y
Rossi-Bergman
B
B
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001483:Base Sequence; D016207:Cytokines / Q000276:immunology*; D017931:DNA Primers / Q000235:genetics; D006084:Graft Rejection / Q000276:immunology*; D007114:Immunization; D016753:Interleukin-10 / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D016038:Skin Transplantation / Q000276:immunology*; D014184:Transplantation, Homologous
D000911:Antibodies, Monoclonal; D016207:Cytokines; D017931:DNA Primers; D016692:Receptors, Antigen, T-Cell, gamma-delta; D016753:Interleukin-10; D015847:Interleukin-4