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R L Edelson

Publications and source records attributed to R L Edelson.

133 records · Page 8Linked to original sources
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Inhibition of antiskin allograft immunity induced by infusions with photoinactivated effector T lymphocytes (PET cells).

Induction of tolerance for skin allotransplantation requires selective suppression of the host response to foreign histocompatibility antigens. This report describes a new approach which employs pre-treatment with 8-methoxypsoralen (8-MOP) and ultraviolet A light (UVA) to render the effector cells of graft rejection immunogenic for the syngeneic recipient. Eight days after BALB/c mice received CBA/j skin grafts, their splenocytes were treated with 100 ng/ml 8-MOP and 1 J/cm2 UVA prior to reinfusion into naive BALB/c recipients. Recipient mice were tested for tolerance to alloantigens in mixed leukocyte culture (MLC), cytotoxicity (CTL), delayed-type hypersensitivity assays (DTH), and challenge with a fresh CBA/j graft. Splenocytes from BALB/c recipients of photoinactivated splenocytes containing the effector cells of CBA/j alloantigen rejection proliferated poorly in MLC and generated lower cytotoxic T-cell responses to CBA/j alloantigens in comparison with sensitized and naive controls and suppressed the MLC and CTL response to alloantigen from sensitized and naive BALB/c mice. In vivo, the DTH response was specifically suppressed to the relevant alloantigen in comparison with controls. BALB/c mice treated in this fashion retained a CBA/j skin graft for up to 42 days post-transplantation without visual evidence of rejection. These results showed that reinfusion of photoinactivated effector cells resulted in an immunosuppressive host response which specifically inhibited in vitro and in vivo responses that correlate with allograft rejection and permitted prolonged retention of histoincompatible skin grafts.

Animals↗
PubMedDate not supplied

Photopheresis: a new therapeutic concept.

Photopheresis, the process by which peripheral blood is exposed in an extracorporeal flow system to photoactivated 8-methoxypsoralen (8-MOP), is a new treatment for disorders caused by aberrant T lymphocytes. It is now a standard therapy for advanced cutaneous T-cell lymphoma and shows promise in the treatment of two autoimmune disorders, pemphigus vulgaris and progressive systemic sclerosis (scleroderma). Additional diseases for which clinical trials are in progress include multiple sclerosis, organ transplant rejection, rheumatoid arthritis, and AIDS. The mechanism of action appears to involve a "vaccination" against the pathogenic T cells, in a clone-specific manner. Photoactivated 8-MOP initiates a cascade of immunologic events by forming covalent photoadducts with nuclear and cell surface-adherent DNA and possibly with other cellular molecules. For reasons not yet fully clarified, but probably related to enhanced cycling of the T-cell receptor for antigen, photopheresis increases the immunogenicity of the irradiated T cells so that their reinfusion induces a therapeutically significant immunologic reaction that targets unirradiated T cells of the pathogenic clone(s). The specificity of the induced immunologic reaction probably results from the extremely disproportionate expansion of the pathogenic clone(s), relative to the several million other clones of normal T cells.

Autoimmune Diseases↗
PubMedDate not supplied

Phototherapy and photopharmacology.

The activation of 8-methoxypsoralen (8-MOP) by long-wavelength ultraviolet A light (UVA, 320-400 nm) induces the formation of interstrand cross-links in DNA. Psoralen plus UVA (PUVA) is widely used in the treatment of psoriasis, a hyperproliferative disease of the skin. A new psoralen plus UVA therapy has been developed in which the 8-MOP-containing blood of cutaneous T cell lymphoma (CTCL) patients is irradiated with UVA light extracorporeally (i.e., extracorporeal photopheresis). The first group of patients had the leukemic variant of CTCL. A regimen of two treatments on successive days at monthly intervals produced a clinical response in eight of 11 patients. In this review the properties of several psoralens (both naturally occurring and synthetic derivatives) are compared, using several assays (DNA cross-linking, inhibition of lymphocyte response to mitogen stimulation, and cell viability). The development of a panel of monoclonal antibodies that recognize 8-MOP-modified DNA is also described. These antibodies have been used to quantitate 8-MOP photoadduct levels in human DNA samples. In addition to the psoralens, the light activation of two other compounds, gilvocarcin and an insulin-psoralen conjugate, is described.

Animals↗