PROLONGATION OF RAT-KIDNEY ALLOGRAFT SURVIVAL BY NEMATODES

Nippostrongylus infection strongly stimulates TH2 activity in vivo. Gi ven the evidence of cross regulation between TH2 and TH1 cells, and th e link between TH1 activity and graft rejection, we examined the effec ts of Nippostrongylus infection on the fate of kidney allografts in ra ts, Both prior Nippostrongylus infection and prior treatment with a so luble worm product significantly delayed kidney allograft rejection. C ontrol graft rejection occurred at 9.7+/-1.2 days whereas grafts in Ni ppostrongylus- or worm extract-treated recipients lasted 32.7+/-11.3 d ays and 21.5+/-4.6 days, respectively. At day 5 posttransplant mononuc lear cell infiltration was much reduced in the Nippostrongylus-treated recipients. Flow cytometry of isolated graft-infiltrating leukocytes showed a marked decrease in infiltrating T cells (82.8% reduction) wit h both CD4(+) cells (81.0% reduction) and CD8(+) cells (84.6% reductio n) being reduced. CD8(+) T cells, in particular, made up a much smalle r proportion of the graft-infiltrating cells (22% rather than 49%) in the Nippostrongylus-treated animals as compared with untreated control s. Immunohistochemical assay of the graft tissue confirmed the flow cy tometric results. Interleukin 4 expression was clearly demonstrated by RT-PCR of the isolated graft-infiltrating leukocytes from the Nippost rongylus-treated recipients but not from the control recipients. These data are consistent with our current hypothesis that Nippostrongylus delays graft rejection by inducing a cross-regulatory suppression of T H1 activity.