We sought to examine the impact of the preferential activation of Th2 cells on the
induction and maintenance of a tolerant state in heart allograft rat recipients treated
with a short course of cyclosporine (CsA), sirolimus (SRL) or brequinar (BQR). A quantitative
polymerase chain reaction (PCR) method was used to measure the levels of cytokine
mRNAs, 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 had 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 +/- 184 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 the 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 from 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 were similar to those of normal
hearts. Grafts from SRL-treated tolerant hosts merely showed slightly increased Th2
cell activity. In conclusion the selective activation of Th2 cells is not absolutely
required for induction or maintenance of tolerance.