Nathan R. York

Immune regulatory CNS-reactive CD8+T cells in experimental autoimmune encephalomyelitis

Immune-based self-recognition and failure to modulate this response are believed to contribute to the debilitating autoimmune pathology observed in multiple sclerosis (MS). Studies from its murine model, experimental autoimmune encephalomyelitis (EAE), have shown that neuroantigen-specific CD4+T cells are capable of inducing disease, while their immune sibling, the CD8+T cells, have largely been ignored. To understand their role in autoimmune demyelination, we first confirmed that, similar to our observations in human MS, there is robust induction of neuroantigen-reactive CD8+T cells in several models, including MOG(35-55)/CFA-induced EAE. However, MOG(35-55)-specific CD8+T-cells, when purified, were unable to adoptively transfer disease into naïve mice (in contrast to CD4+T-cells). In fact, we observed that the transfer of these neuroantigen-specific CD8+T cells was able to suppress the induction of EAE and to inhibit ongoing EAE. These regulatory CD8+T cells produced IFN-gamma and perforin and were able to kill MOG loaded CD4+T-cells as well as CD4-depleted APC, suggesting a cytotoxic/suppressor mechanism. Inhibition of EAE was associated with both the modulation of APC function as well as decreased MOG-specific CD4+T cell responses. Our studies reveal a novel and unexpected immune regulatory function for neuroantigen-specific CD8+T cells and have interesting biologic and therapeutic implications.

UVA1 phototherapy: a review of mechanism and therapeutic application

Ultraviolet radiation (UVR) phototherapy has been associated with both deleterious and beneficial effects to patients with both localized and systemic skin disorders. Phototherapy is advantageous in diseases of the epidermis and dermis, as it provides the most direct approach minimizing systemic side effects. Most recently, ultraviolet A1 (UVA1) phototherapy has emerged as a specific UVR phototherapeutic mechanism. It has shown to be therapeutic in a number of sclerosing skin conditions and other dermatitides, in many cases proving to be more effective than other phototherapy modalities. Treatment advantages of UVA1 phototherapy include the ability to penetrate into the deep layers of the skin to affect changes on disease‐causing T cells, as well as activation of endothelial cells to promote neovascularization. UVA1 therapy also has been shown to be relatively free of side effects associated with other phototherapy regimens, including erythema and cellular transformation. These properties make UVA1 phototherapy an important treatment option for many debilitating skin conditions.

Drug-induced linear IgA bullous dermatosis demonstrating the isomorphic phenomenon.

negative. No fungi were seen with PAS staining, and ZiehleNeelsen staining was negative for mycobacteria. No viral inclusions or birefringent foreign material were seen. These findings were consistent with a diagnosis of malakoplakia. Screening blood tests have shown a normal full blood count, renal and liver profile, a negative rheumatoid factor, antinuclear antibody, and antineutrophil cytoplasmic antibody. It is believed that malakoplakia represents an unusual granulomatous response to bacterial infection, in which macrophages fail to phagocytose bacteria properly. It may be that an infraabdominal skin fold habors organisms like other intertriginous areas—hence the development of malakoplakia in this site. Histopathologically, malakoplakia is characterized by sheets of large histiocytic cells with abundant cytoplasm containing fine eosinophilic granules (von Hansemann cells). Some cells contain rounded, laminated basophilic inclusion bodies (Michaelise Gutmann bodies) which stain positively with PAS, von Kossa stain (for calcium), and Perl iron stain. These MichaeliseGutmann bodies are pathognomonic for malakoplakia and are thought to represent calcified remnants of bacterial cell walls secondary to inadequate killing and digestion of bacteria. The skin lesions of malakoplakia tend to be persistent, and a multitude of treatments have been reported, though none are satisfactory. These include protracted courses of antibiotics, ascorbic acid and bethanechol chloride, excision of localized disease, and reducing the dose of immunosuppressive therapy or treating the cause of any underlying immunosuppression. Our case highlights a rarity amongst a rarity; a previously healthy person with cutaneous malakoplakia in an infraabdominal skin fold with no previous history of surgery or immunosuppression. Her lesions have persisted, though less floridly than initially, and it is unclear as to whether the topical anticandidal treatment has aided this.