Ultraviolet Radiation-Induced Impairment of the Early Initiating and the Late Effector Phases of Contact Hypersensitivity to Picrylcholoride: Regulation by Different Mechanisms

Two types of antigen-specific T cells are needed for the elicitation of contact hypersensitivity reactions. They act in an obligate sequence to mediate the early initiating and late effector phases of contact hypersensitivity, which are accompanied by skin-swelling responses at 2 and 24h after challenge, respectively. The magnitude of the late ear swelling depends on that of the early swelling.We studied the influence of ultraviolet radiation on both phases of contact hypersensitivity to picrylchloride. Mice were exposed to subedemal doses of ultraviolet radiation on the shaved backs for four consecutive days. Four days later mice were sensitized on non-irradiated skin. Four days after sensitization mice were challenged on the ears, and swelling was measured 2, 4, and 24h after challenge. The early and late phases of contact hypersensitivity were largely suppressed in ultraviolet-irradiated, actively sensitized mice. Transfer of immune lymphoid cells from donor mice that were sensitized 4 d earlier induced early and late components of contact hypersensitivity in naive recipients after challenge. Transfer of immune lymphoid cells from donors that were sensitized 1 d earlier only induced the early component of contact hypersensitivity. Ultraviolet irradiation of donor mice significantly reduced the capacity of the immune lymphoid cells to induce contact hypersensitivity. We show that lymphoid cells responsible for the early and late components of contact hypersensitivity are both affected

Cells with UV-Specific DNA Damage Are Present in Murine Lymph Nodes After In Vivo UV Irradiation

Ultraviolet radiation is absorbed in the skin, especially in the epidermis. After ultraviolet irradiation the number of major histocompatibility complex class II+, adenosine triphosphatase+ Langerhans cells and Thy-1+ dendritic epidermal cells in the epidermis decreases. Whether this decrease is due to migration of these cells or to loss of membrane markers is not clear. To address this question we have used the monoclonal antibody H3 directed against cyclobutyl thymine dimers – a form of DNA damage that is specifically induced by ultraviolet radiation – to investigate whether H3+ cells are present in the draining lymph nodes of the skin after ultraviolet irradiation of hairless, inbred mice (HRA/Skh). After a single dose of ultraviolet radiation (Westinghouse FS40, 1.5 kJ/m2), H3+ cells were present in the paracortex of the draining lymph nodes. No positive cells were found in t:he blood of irradiated mice. These results suggest that the H3+ cell in the lymph nodes originate from the skin. The number H3+ cells in the draining lymph nodes increased the first 24 h after irradiation and then stabilized. Immunohistochemical double staining revealed that all H3+ cells were major histocompatibility complex II+, and that only a fraction of the cells were NLDC-145 positive. No Vγ3-cell receptor bearing cells could be found in the lymph nodes after UV irradiation of the skin

Association of transcription-coupled repair but not global genome repair with ultraviolet-B-induced Langerhans cell depletion and local immunosuppression.

Exposure to ultraviolet-B radiation impairs cellular immune responses. This immunosuppression seems to be associated with Langerhans cell migration. DNA damage appears to play a key role because enhanced nucleotide excision repair, a pathway essential for elimination of ultraviolet-B-induced DNA lesions, strongly counteracts immunosuppression. To determine the effect of DNA repair on ultraviolet-B-induced local immunosuppression and Langerhans cell disappearance, three mouse strains carrying different defects in nucleotide excision repair were compared. XPC mice, which were defective in global genome repair, were as sensitive to ultraviolet-B-induced local suppression of contact hypersensitivity to picryl chloride as their wild-type littermates. CSB mice, defective in transcription-coupled repair, were far more sensitive for immunosuppression as were XPA mice, defective in both transcription-coupled repair and global genome repair. Only a moderate depletion of Langerhans cells was observed in XPC mice and wild-type littermates. Ultraviolet-B-induced Langerhans cell depletion was enhanced in CSB and XPA mice. Hence, the major conclusion is that local immunosuppression is only affected when transcription-coupled DNA repair is impaired. Furthermore, a defect in transcription-coupled repair was linked to enhanced ultraviolet-B-induced Langerhans cell depletion. In combination with earlier experiments, it can be concluded that Langerhans cell disappearance is related to ultraviolet-B-induced local but not to systemic immunosuppression

The glucagonoma syndrome and necrolytic migratory erythema: A clinical review

The glucagonoma syndrome is a rare disease in which a typical skin disorder, necrolytic migratory erythema, is often one of the first presenting symptoms. Weight loss and diabetes mellitus are two other prevalent characteristics of this syndrome. Necrolytic migratory erythema belongs to the recently recognized family of deficiency dermatoses of which zinc deficiency, necrolytic acral erythema and pellagra are also members. It is typically characterized on skin biopsies by necrolysis of the upper epidermis with vacuolated keratinocytes. In persistent hyperglucagonemia, excessive stimulation of basic metabolic pathways results in diabetes mellitus at the expense of tissue glycogen stores, and muscle and fat mass. Multiple (essential) nutrient and vitamin B deficiencies develop, which contribute to the dermatosis. In addition, glucagonomas may produce various other products, like pancreatic polypeptide, that add to the catabolic effects of glucagon. © 2004 Society of the European Journal of Endocrinology