Abstract

Acute GVHD is induced by allo-reactivity of donor T cells towards host antigens presented on antigen presenting cells (APCs). Apoptotic cells are capable of inducing tolerance by altering APC maturation. Apoptosis can be induced by extracorporeal photopheresis (ECP). We demonstrate that the use of ECP as a prophylaxis prior to conditioning significantly improves survival (p<0.0001) after bone marrow transplantation (BMT) by inhibiting the initiation phase of acute GVHD in a murine BMT model. ECP-treated autologous splenocytes resulted in immune tolerance in the host, including reduced dendritic cell activation with decreased NF-?B engagement, increased regulatory T cell numbers (Treg) with enhanced expression of CTLA4, potentiating their suppressive function. The protective effect required host-production of IL-10 and host Tregs. Conventional T cells that entered this tolerant environment experienced reduced proliferation, as well as a reduction of tissue homing and expression of activation markers. The induction of this tolerant state by ECP was obviated by co-treatment with LPS, suggesting that the inflammatory state of the recipient prior to treatment would play a role in potential clinical translation. The use of prophylactic ECP may provide an alternative and safe method for immunosuppression in the bone marrow transplant setting.

View details for DOI 10.1182/blood-2014-02-555128

View details for Web of Science ID 000342762600019