Cd45rc- γδ+ T–Cell Infiltration Is Associated With Immunologic Unresponsiveness Induced by Prior Donor–Specific Blood Transfusion in Rat Hepatic Allografts

Abstract

Little is known regarding the role of gammadelta(+) T cells in organ transplantation. We previously reported that immunologic unresponsiveness is induced by prior donor-specific blood transfusion (DST) in rat hepatic allografts. We investigated the phenotype and distribution of gammadelta(+) T cells in the hepatic allograft, spleen, and peripheral blood of recipient rats with immunologic unresponsiveness induced by DST. gammadelta(+) T cells were enumerated in allograft livers and spleens by immunostaining and in blood by flow cytometric analysis. The phenotype of gammadelta(+) T cells was determined using CD45RC isoforms derived from alternative mRNA splicing. The cytokine profile of CD45RC(+) and CD45RC(-) gammadelta(+) T cells was analyzed by reverse transcription polymerase chain reaction. The number of gammadelta(+) T cells in hepatic infiltrates in recipient rats pretreated with DST was significantly greater than in untreated animals. This correlated with significantly higher levels of gammadelta T cell receptor (TCR) mRNA in hepatic allografts of DST-treated rats as compared with untreated animals. The gammadelta(+) T cell/alphabeta(+) T-cell ratio increased in hepatic infiltrates in DST-treated recipient rats but not in untreated animals. CD45RC(-)gammadelta(+) T cells were predominantly increased in DST-treated hepatic allografts compared with untreated allografts. Most of the intestinal intraepithelial T cells were CD45RC(-)gammadelta(+). Interleukin (IL)-10 and IL-4 mRNA were detected more in CD45RC(-)gammadelta(+) T cells than CD45RC(+)gammadelta(+) T cells. CD45RC(-)gammadelta(+) T cells infiltrating liver allografts produce Th2-type cytokines and are associated with immunologic unresponsiveness induced by DST.