Achieving long-term allograft survival or tolerance without continuously global immunosuppression is a highly desirable goal. This study is to induce long-term allograft survival without long-term conventional immunosuppression via short-term treatments with traditional Chinese medicine, which is generally accepted to generate less side-effects. Chinese herbs Cornus officinalis (CO) and Cuscuta sinensis Lam (CSL) have been shown to be effective in treating some autoimmune diseases according to previous experience in clinical Chinese medicine. In this study, C57BL/6 mice were transplanted with a Balb/C skin and treated with CO and/or CSL (5mg/Kg/Day orally for 3-4 weeks). CD4+FoxP3+ Tregs were determined by FACS while draining LN T cell proliferation was measured by the BrdU labeling. The used doses of CO and CSL did not result in any toxic injury to kidneys and livers of recipients as evident by histology, and UFLC fingerprinting indicated that these two herbs did not contain cyclosporine and rapamycin.

We found that CO dramatically extended skin allograft survival compared with control group (MST = 34 vs. 13 days, n=7-8, P<0.05) while CSL also delayed the rejection with a statistical significance (MST = 23 vs. 13 days, n=7-8, P<0.05). Importantly, treatments with both CO and CSL further prolonged skin allograft survival (MST = 65 versus 13 days, n=7-9, P<0.05), with 44% of recipient mice achieving long-term allograft survival (>100 days). Moreover, either CO or CSL suppressed draining LN T cell proliferation two week after transplantation (CO: BrdU+: 27±3 vs. 43±4 %, P<0.05; and CSL: BrdU+: 31±3 vs. 43±4 %, P<0.05) while CO plus CSL further inhibited T cell proliferation (BrdU+: 15±2 vs. 43±4 %, P<0.05). However, CO did not increase CD4+FoxP3+ Treg numbers in the draining LN (2.9±0.5 vs 2.5±0.4, x10000, P>0.05) while CSL did so (4.0±0.6 vs 2.5±0.4, P<0.05). CO plus CSL further increased the Treg number compared to CSL alone (5.7±0.5 vs. 4.0±0.6, P<0.05). Thus, for the first time, our studies demonstrate that Chinese herbs CO and CSL synergistically promote long-term allograft survival in the absence of conventional immunosuppressant although CO is primarily immunosuppressive while CSL mainly induces FoxP3+ Tregs.

« Back to 2015 American Transplant Congress