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)F1 (LBNF1) 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 LBNF1 spleen cells. As reported earlier, in rats with pv drained grafts there was an increase in gammadeltaTCR+ cells infiltrating the Peyer's patches (PP) and mesenteric lymph node (MLN) compared with iv drained grafts. After restimulation in culture with irradiated LBNF1 spleen stimulator cells these PP and MLN cells from SIT rats with pv graft drainage were a prominent source of TGFbeta, IL-4, and IL-10. When subpopulations of cells from PP preparations were analyzed, an enriched (<2%betaTCR+) gammadeltaTCR+ population from SIT rats with pv graft drainage, but not iv drainage, was detected that suppressed in vitro type-1 cytokine production (IL-2, IFNgamma) from alphabetaTCR+ (<2%gammadeltaTCR+) cells derived from the MLN or peripheral lymph nodes (PLN) of these same animals. On adoptive transfer to naive LEW rats simultaneously receiving LBNF1 SIT, gammadeltaTCR+ 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-gammadeltaTCR 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 gammadeltaTCR+ cells in the regulation of graft rejection in this model.
Gorczynski
R M
RM
Multi-Organ Transplant Program, The Toronto Hospital, Ontario, Canada.
Cohen
Z
Z
Levy
G
G
Fu
X M
XM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology; D006085:Graft Survival; D007421:Intestine, Small / Q000098:blood supply / Q000276:immunology / Q000637:transplantation*; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D008222:Lymphokines / Q000378:metabolism; D010581:Peyer's Patches / Q000276:immunology / Q000473:pathology; D011169:Portal Vein; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D014184:Transplantation, Homologous; D014682:Vena Cava, Inferior
D000911:Antibodies, Monoclonal; D008222:Lymphokines; D016692:Receptors, Antigen, T-Cell, gamma-delta