L. Tian et al., CYTOKINE MESSENGER-RNA EXPRESSION IN TOLERANT HEART ALLOGRAFTS AFTER IMMUNOSUPPRESSION WITH CYCLOSPORINE, SIROLIMUS OR BREQUINAR, Transplant immunology, 5(3), 1997, pp. 189-198
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.