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Intragraft cytokine expressionf in tolerant rat renal allografts with rapamycin and cyclosporin immunosuppression
Author(s) -
Saggi Bh,
Fisher Ra,
Naar Jd,
Bu D,
Obias V,
Tawes Jw,
Wakely Jr Paul E,
Posner Mp
Publication year - 1999
Publication title -
clinical transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 76
eISSN - 1399-0012
pISSN - 0902-0063
DOI - 10.1034/j.1399-0012.1999.130105.x
Subject(s) - immunosuppression , medicine , transplantation , kidney , immune tolerance , cytokine , immunology , kidney transplantation , mixed lymphocyte reaction , t cell , immune system
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 Lewis rats were used as donors and recipients, respectively, for heterotopic renal transplantation. Group A (n=8) received a single dose of rapamycin and cyclosporin 12 h prior to engraftment, followed by 7 d of cyclosporin post‐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‐10, IL‐4, and IFN‐ Γ was determined using qualitative reverse transcriptase‐polymerase chain reaction (RT‐PCR). All groups had functionally normal grafts at sacrifice, with 50% histological tolerance among Group A animals. No isografts showed evidence of cellular infiltrate, 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‐ Γ was only isolated in rejected allografts, whether treated or untreated (p<0.001). We conclude that the expansion of Th‐2 cells is associated with tolerance, while the expansion of Th‐1 cells is associated with acute cellular rejection.