*Purpose: Induction of long-term transplant survival without continuous global immunosuppression is a highly desired goal in transplantation. Electroacupuncture (EA) has been shown to regulate immunity and inhibit inflammation. However, it’s unknown whether EA also modulates alloimmunity. The objective of this study is to determine if EA inhibits allograft rejection.

*Methods: B6 mice were transplanted with either islets or skin from Balb/C donors. Recipient mice were treated without or with rapamycin (0.4 mg/kg/day) and/or EA at Zusanli or EA adjacent to allografts (6V/20Hz, 15 min daily). Lymphotoxin α (LTα)-deficient or WT mice were used as recipients while LTα-replete or LTα-deficient Tregs were transferred to Rag1-/- mice receiving CD4+CD25- T cells and islet allografts to define the role for LTα in Treg suppression. Synthesized peptide ciLT was administered to block LTα1β2/ LTβR interaction. Graft-infiltrating and draining LN cells were isolated to measure LTα1β2 expression by Tregs via FACS. Tregs in draining LNs were quantified via FACS while Tregs in lymphatics were measured via immunofluorescence.

*Results: We found that EA at regular Zusanli alone did not prolong islet allograft survival. Surprisingly, EA adjacent to allografts (EAA) moderately extended survival of islet allografts (MST = 25 vs. 14 days, P<0.05) but not skin allografts (MST = 16 vs. 13 days, P>0.05). Importantly, EAA plus rapamycin further prolonged islet allograft survival compared to EAA alone (MST = 85 vs. 25 days, P<0.05) or rapamycin alone (MST = 85 vs. 44 days, P<0.05), with 50% of recipients achieving long-term islet allograft survival (>90 days). EAA plus rapamycin further extended skin allograft survival compared to EAA alone (MST = 56 vs.16 days, P<0.05) or rapamycin alone (MST = 56 vs. 31 days, P<0.05). Moreover, EAA increased FoxP3+ cell numbers within lymphatics in skin grafts compared to control (6.3±0.5 vs. 3.1±0.2/screen, P<0.05), while it augmented their numbers in draining LNs (2.2±0.2 vs. 1.0±0.1, x10000 /LN, P<0.05). Interestingly, EAA increased LTα1β2 expression by Tregs in the grafts (MFI: 279±23 vs. 121±14, P<0.05) and draining LNs (MFI: 258±21 vs. 115±13, P<0.05). Blocking LTα1β2/ LTβR interaction with peptide ciLT reversed an EAA-induced increase of FoxP3+ cell numbers in lymphatics (3.5±0.4 vs. 3.3±0.2/control, P>0.05) and EAA-extended islet allograft survival (MST = 16 vs. 14 days/control, P>0.05). EAA also failed to prolong islet allograft survival in LTα-/- mice. Finally, transfer of LTα-replete but not LTα-deficient Tregs prolonged islet allograft survival in Rag1-/- mice.

*Conclusions: EAA itself extended islet, but not skin, allograft survival while EAA and rapamycin synergistically prolonged skin allograft survival and induced long-term islet allograft survival. Its effects were dependent on its upregulation of LTα1β2 expression on Tregs and Treg migration into lymphatics.

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