Regulatory T Cells and Ocular Graft Versus Host Disease: A Novel Treatment Approach

Abstract Graft Versus Host Disease (GVHD) is an inflammatory immune disease, mediated by the donor’s immune cells and can arise after allogeneic Hematopoietic Stem Cell Transplantation (HSCT) for the treatment of hematologic malignancies. It can lead to destructive manifestations in various tissues, particularly dermatological, gastrointestinal, and ocular tissues. The most common ocular morbidity is dry eyes, which is often the first manifestation of GVHD. Regulatory T cells (Tr) can be broadly classified as natural or adaptive (induced). After Bone-Marrow Transplantation (BMT), excessively increased levels of type ۱ Tr (Tr۱) are generally observed with absence of a GVHD, while low levels are seen with severe GVHD. Treatment of patients, undergoing BMT with Interleukin-۱۰ (IL-۱۰)-anergized donor T cells, led to immune reconstitution without the development of GVHD, which resulted in protection against infection and against the return of the cancer. Surprisingly, in both naive syngeneic mouse models of skin and cardiac allografts, graft retention was augmented after infusion of in vitro generated double-negative Tr (DN Tr). In addition, GVHD was reduced in mice with a genetic deficiency in the IL-۲۷ receptor (IL-۲۷R-/-) and in mice treated with anti-IL-۲۷p۲۸–specific antibody. Considering above mentioned findings we would suggest carrying out experiments, using animal models of GVHD, in order to evaluate the potential role of Tr, as an innovative approach to overcome severe ocular morbidity caused by ocular GVHD.