A role for gamma delta TCR(+) cells in regulation of rejection of small intestinal allografts in rats

Lewis (LEW) rats received (Lewis x Brown Norway)F-1 (LBNF(1)) small intestinal allografts (SIT) with graft venous drainage to either the portal vein (pv) or inferior vena cava (iv), along with immunization (pv or iv) with irradiated LBNF(1) spleen cells, As reported earlier, in rats with pv drained grafts there was an increase in gamma delta TCR(+) cells infiltrating the Peyer's patches (PP) and mesenteric lymph node (MLN) compared with iv drained grafts, After restimulation in culture with irradiated LBNF(1) spleen stimulator cells these PP and MLN cells from SIT rats with pv graft drainage were a prominent source of TGF beta, IL-4, and IL-10. When subpopulations of cells from PP preparations were analyzed, an enriched (<2%alpha beta TCR(+)) gamma delta TCR(+) population from SIT rats with pv graft drainage, but not iv drainage, was detected that suppressed in vitro type-1 cytokine production (IL-2, IFN gamma) from alpha beta TCR(+) (alpha beta TCR(+)) cells derived from the MLN or peripheral lymph nodes (PLN) of these same animals. On adoptive transfer to naive LEW rats simultaneously receiving LBNF, SIT, gamma delta TCR(+) enriched PP cells from these primary donors (pv immunized, SIT rats with pv graft drainage) produced prolonged graft/animal survival compared with PP cells obtained from primary donors that had iv drained grafts, In addition, simultaneous infusion of anti-gamma delta TCR monoclonal antibody into SIT rats with pv graft drainage blocked the graft enhancement normally seen in these animals, These data are consistent with an important role for type-2 cytokine producing gamma delta TCR(+) cells in the regulation of graft rejection in this model.