Aim Naïve CD4+CD25+Foxp3+Treg activated by specific alloantigen (alloAg) and IL-4, not IL-2, express the specific IL-5 receptor (Ts2 cells). Ts2 cells are more potent alloAg specific Treg than nTreg. Here we examined if IL-5Rx activated alloAg specific Ts2 cells to prevent chronic rejection.
Methods F334 recipients with Lewis heart grafts received 5000units rIL-5 ip daily for 10d from 7d after grafting. Rejection was scored on a semi-quantitative scale.
Results Sham Rx rats developed rejection at 18d (mean score of +++) and all rejected by 28d(n=5). IL-5Rx prevented rejection, with all grafts ++++-+++ until cessation of IL-5Rx at day 18(p<0.01 vs sham Rx). After 18d, there was rejection (mean score ++) until 50d(n=5)(p<0.01). Another group continued IL-5Rx 3x/week from 18(n=5), had transient rejection a few days after changing to 3x/week, but by 30d grafts recovered with 3 of 5 ++++, one +++ and one ++ at 60d (p<0.05 vs short IL-5Rx; p<0.01 vs sham Rx).
IL-5Rx had increased CD4+CD25+T cells to 6-8% vs 3-4% in controls and normal. At 18d after 10d of IL-5Rx, CD4+CD25+T cells responded to Lewis but not to F344 or third party PVG, showing activation of alloAg specific Treg by IL-5Rx. CD4+CD25+T cells from rats treated 50d with IL-5 showed response to Lewis was enhanced by IL-5.
Conclusion IL-5 is known to promote growth of Ag specific Ts2 cells that may prevent rejection. IL-5Rx induced Ag specific Ts2 cells and long term treatment ensured good graft function. This therapy may have potential to prevent chronic allograft rejection.