![Sample our Medicine, Dentistry, Nursing & Allied Health journals, sign in here to start your FREE access for 14 days]({"type":"image" , "src" : "/sda/5944/TOC-Subject-Sample-2021-Medicine-Dentistry-Nursing-Allied-Health.jpg"})
Abstract
Infusions of syngeneic T-cells, lethally damaged with ultraviolet A light (UVA) and 8-methoxypsoralen (8-MOP), have been reported to prevent or ameliorate a number of autoimmune diseases in humans and in animal models of autoimmune disease. We previously demonstrated that the combination of UVA/8-MOP, or deoxycoformycin and deoxyadenosine (dCF/dAdo), damaged human lymphoid cells by inducing DNA strand breakage and stimulating poly (ADP-ribosyl)ation. These cells subsequently underwent programmed cell death (“apoptosis”). These findings suggested a common mechanism of lymphocyte damage, and that in vitro treatment of T-cells with cCF/dAdo might substitute for UVA/8-MOP. This hypothesis was tested in a model of autommune diabetes in the NOD mouse. Young adult female NOD/Wehi mice were given 350 mgAg cyclophosphamide (CP) on day 1 to induce rapid-onset diabetes and divided into five treatment groups. Four groups received approximately 50x106 syngeneic mouse splenocytes that had been treated with various cytotoxic agents. 27/40 (68%) of the CP-only control group and 14/30 (48%) of the group given untreated splenocytes developed diabetes. By contrast, only 2/20 (10%) mice of UVA/8-MOP and 3/23 (14%) of dCF/dAdo-treated splenocyte groups developed diabetes (P<0.01). Diabetes in high spontaneous-diabetes incidence NOD/Lt female mice was also greatly reduced (4/8 untreated vs 1/7 treated;(<0.05). We postulate that cytotoxic damage to activated splenic T-cells allows their recognition by host T-cells and results in a protective response against autoreactive cells as a form of T-cell vaccination. We further suggest that extracorporeal photochemotherapy may be able to be replaced by leukapheresis and in vitro exposure of buffy coat lymphocytes to DNA-damaging cytotoxic agents such as dCF/dAdo.