Intragraft cytokine expression in tolerant rat renal allografts with rapamycin and cyclosporin immunosuppression

The Th-1/Th-2 paradigm proposes clonal expansion of Th-2 lymphocytes as the basis of tolerance towards allografts. Intragraft cytokine expression was evaluated in a highly stringent model of renal transplantation. ACI and Lew is rats were used as donors and recipients, respectively, for heterotopic r enal transplantation. Group A (n = 8) received a single dose of rapamycin a nd cyclosporin 12 h prior to engraftment, followed by 7 d of cyclosporin po st-operatively. Isografts (Group B, n = 5) and control allografts (Group C, n = 4) received no immunosuppression. Sacrifice was performed after 120 d. Intragraft expression of IL-IO, IL-4, and IFN-gamma was determined using q ualitative reverse transcriptase-polymerase chain reaction (RT-PCR). All gr oups had functionally normal grafts at sacrifice, with 50% histological tol erance among Group A animals. No isografts showed evidence of cellular infi ltrate, and all control allografts showed severe rejection. IL-10 was only detected in the tolerant animals (p < 0.001). Similarly, IL-4 was detected predominantly in the tolerant allografts (p ( 0.05). IFN-gamma was only iso lated in rejected allografts, whether treated or untreated (p < 0.001). We conclude that the expansion of Th-2 cells is associated with tolerance, whi le the expansion of Th-1 cells is associated with acute cellular rejection.