CYTOKINE MESSENGER-RNA EXPRESSION IN TOLERANT HEART ALLOGRAFTS AFTER IMMUNOSUPPRESSION WITH CYCLOSPORINE, SIROLIMUS OR BREQUINAR

We sought to examine the impact of the preferential activation of Th2 cells on the induction and maintenance of a tolerant state in heart al lograft rat recipients treated with a short course of cyclosporine (Cs A), sirolimus (SRL) or brequinar (BQR). A quantitative polymerase chai n reaction (PCR) method was used to measure the levels of cytokine mRN As, namely interferon (IFN)-gamma and interleukin (IL)-2 in T helper 1 (Th1) cells and IL-4, IL-5 and IL-10 in Th2 cells. Our main findings were that on day 5 postgrafting allografts from untreated recipients h ad increased levels of IFN-gamma(216 +/- 119 fg), IL-2 (449 +/- 75 fg) , IL-4 (6.2 +/- 1.3 fg), IL-5 (34.8 +/- 9.3 fg) and IL-10 (1554 +/- 18 4 fg) mRNAs compared with normal hearts. CsA reduced the levels of IFN -gamma IL-2, IL-5 and IL-10, but not IL-4, mRNAs. SRL did not affect t he expression of cytokine mRNAs. BQR decreased the levels of IFN-gamma , IL-2 and IL-10, but not IL-5 or IL-4 mRNAs. Compared with grafts fro m untreated recipients, those from CsA- or BQR-treated tolerant hosts (day 100) displayed undetectable IL-2 mRNA levels, and reduced levels of IFN-gamma, IL-4 and IL-10 mRNAs. In fact, the patterns of cytokine mRNA expression in grafts from CsA- and BQR-treated tolerant hosts wer e similar to those of normal hearts. Grafts from SRL-treated tolerant hosts merely showed slightly increased Th2 cell activity. In conclusio n the selective activation of Th2 cells is not absolutely required for induction or maintenance of tolerance.