IL-33 prolongs murine cardiac allograft survival through induction of TH2-type immune deviation.
BACKGROUND
In Th (T helper) 1/Th2 balance in response to signals given during donor antigen presentation, induction of allograft prolongation is more often related to Th2-type than with Th1-type immunity. Here, we examined the effect of interleukin (IL)-33, a novel member of the IL-1 family, on cardiac allograft survival in mice.


METHODS
Mice heterotopic cardiac transplants were performed with sequential recipient sacrifice at anticipated time points to examine the immunoregulatory action of IL-33 in recipient mice.


RESULTS
In vitro Th1-polarized CD4 T cells did not express ST2L; however, most CD4 T cells became ST2L on repeated stimulation under Th2-polarizing conditions. Similarly, we found that IL-33 was able to enhance the expression of Th2-associated cytokines (IL-5 and IL-13) but not interferon (IFN)-gamma. Treatment of recipient mice with IL-33 results in the improvement of allograft survival (more than 20 days) when compared with phosphate-buffered saline- or glutathione S-transferase-treated groups (all less than 9 days). Intracellular cytokine staining in CD4 splenocytes confirmed an increase in the percentage of IL-4 cells and a decrease in the percentage of IFN-gamma cells in IL-33 treated mice. In addition, IL-33 significantly enhanced the gene expression of Th2-type cytokines IL-4 and IL-5 but suppressed the Th1-type cytokine IFN-gamma mRNA levels in both allograft and recipient spleen.


CONCLUSIONS
These data demonstrate that IL-33 serves as a potent inducer of Th2 immune response and can markedly contribute to the prolongation of cardiac allograft survival.
Yin
Hui
H
Department of Microbiology and Immunology, Guangdong Pharmaceutical University, Guangzhou, China.
Li
Xiang-Yong
XY
Jin
Xiao-Bao
XB
Zhang
Bo-Bin
BB
Gong
Quan
Q
Yang
Heng
H
Zheng
Fang
F
Gong
Fei-Li
FL
Zhu
Jia-Yong
JY
D000818:Animals; D001483:Base Sequence; D016764:Cell Polarity; D017931:DNA Primers; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate; D005784:Gene Amplification; D006085:Graft Survival / Q000187:drug effects* / Q000276:immunology; D016027:Heart Transplantation / Q000276:immunology / Q000379:methods / Q000502:physiology*; D000067596:Interleukin-33; D007378:Interleukins / Q000235:genetics / Q000627:therapeutic use*; D007518:Isoantibodies / Q000097:blood / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins / Q000627:therapeutic use; D013154:Spleen / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology / Q000502:physiology; D018418:Th2 Cells / Q000276:immunology* / Q000502:physiology; D014184:Transplantation, Homologous
D017931:DNA Primers; C506535:Il33 protein, mouse; D000067596:Interleukin-33; D007378:Interleukins; D007518:Isoantibodies; D011994:Recombinant Proteins; D016650:Fluorescein-5-isothiocyanate