Application Of Contact Allergen Research Articles

Oral tolerance to contact allergens: a common occurrence? A review

Experimental and clinical oral tolerance to contact allergens has been reported sporadically, most notably in respect of nickel, and is generally assumed to be an uncommon phenomenon. There has recently been increased understanding of the immunological mechanisms inducing and maintaining oral tolerance. There are several contact allergens, including fragrance, antioxidant, and preservative chemicals, to which subjects are exposed through both cutaneous and oral routes. We examine the possibility that oral tolerance to contact allergens may be more common than previously thought. Animal models of oral tolerance to contact allergens indicate that cutaneous exposure to small, subsensitizing doses of contact allergens might negate any subsequent attempts to induce tolerance by oral administration. Extrapolating these observations to common human practises raises the possibility that application of contact allergens (fragrances, preservatives and antioxidants) in consumer products used by children could prevent or inhibit the later acquisition of specific tolerance resulting from 'natural' dietary exposure after weaning. Existing data on formaldehyde may conflict with this theory, though this could be explained by allergen specificity. We propose that further work in this area is needed.

Mechanisms of UV-induced immunosuppression

Ultraviolet radiation (UV), in particular the UVB range, suppresses the immune system in several ways. UVB inhibits antigen presentation, induces the release of immunosuppressive cytokines and causes apoptosis of leukocytes. UVB, however, does not cause general immunosuppression but rather inhibits immune reactions in an antigen-specific fashion. Application of contact allergens onto UV-exposed skin does not cause sensitization but induces antigen-specific tolerance since such an individual cannot be sensitized against the very same allergen later, although sensitization against other allergens is not impaired. This specific immunosuppression is mediated by antigen-specific suppressor/ regulatory T cells. UVB-induced DNA damage is a major molecular trigger of UV-mediated immunosuppression. Reduction of DNA damage mitigates UV-induced immunosuppression. Likewise interleukin-12 which exhibits the capacity to reduce DNA damage can prevent UV-induced immunosuppression and even break tolerance. Presentation of the antigen by UV-damaged Langerhans cells in the lymph nodes appears to be an essential requirement for the development of regulatory T cells. Studies addressing the molecular mechanisms underlying UV-induced immunosuppression will contribute to a better understanding how UV acts as a pathogen but on the other hand can be also used as a therapeutic tool.

Ultraviolet radiation-induced tolerance.

Ultraviolet (UV) radiation is one of the most important environmental factors. Besides its well-known advantages and its indispensable effects on human life, UV light, particularly the middle wavelength range (290-320 nm [UVB]), can harm human health by inducing skin cancer, premature skin aging, inflammation, and cell death (1-4). Over the last 25 years, it has become apparent that exposure to UVB radiation may also suppress immune reactions. Review of the numerous studies on the immunosuppressive properties of UV radiation led to two quite surprising observations: 1) that UV exposure can have systemic immunologic consequences 2) that UV radiation can induce antigen-specific tolerance. This paper briefly reviews the phenomenon of UV-induced tolerance.

Entry Into Afferent Lymphatics and Maturation In Situ of Migrating Murine Cutaneous Dendritic Cells

An important property of dendritic cells (DC), which contributes crucially to their strong immunogenic function, is their capacity to migrate from sites of antigen capture to the draining lymphoid organs. Here we studied in detail the migratory pathway and the differentiation of DC during migration in a skin organ culture model and, for comparison, in the conventional contact hypersensitivity system. We report several observations on the capacity of cutaneous DC to migrate in mouse ear skin. (i) Upon application of contact allergens in vivo the density of Langerhans cells in epidermal sheets decreased, as determined by immunostaining for major histocompatibility complex class II, ADPase, F4/80, CD11b, CD32, NLDC-145/DEC-205, and the cytoskeleton protein vimentin. Evaluation was performed by computer assisted morphometry. (ii) Chemically related nonsensitizing or tolerizing compounds left the density of Langerhans cells unchanged. (iii) Immunohistochemical double-staining of dermal sheets from skin organ cultures for major histocompatibility complex class II and CD54 excluded blood vessels as a cutaneous pathway of DC migration. (iv) Electron microscopy of organ cultures revealed dermal accumulations of DC (including Birbeck granule containing Langerhans cells) within typical lymphatic vessels. (v) Populations of migrating DC in organ cultures upregulated markers of maturity (the antigen recognized by monoclonal antibody 2A1, CD86), but retained indicators of immaturity (invariant chain, residual antigen processing function). These data provide additional evidence that during both the induction of contact hypersensitivity and in skin organ culture, Langerhans cells physically leave the epidermis. Both Langerhans cells and dermal DC enter lymphatic vessels. DC mature while they migrate through the skin.

Functional and morphological characterization of 4F7+ spleen accessory dendritic cells.

Recently we have reported on the production of the mAb 4F7. This recognizes a molecule that is upregulated on dermal and epidermal dendritic cells after application of contact allergen. Furthermore, this antibody detects an antigen on spleen and lymph node dendritic cells. In this study, we characterize 4F7+ spleen dendritic cells and show that the mAb recognizes in situ few labeled cells in the white pulp of the spleen and approximately 1% of spleen single cell suspensions as evidenced by cell enrichment, immunoperoxidase staining and FACS analysis. Immunohistological characterization of the cells with mAbs revealed the expression of class II, class I MHC antigens, 33D1, CD11c, ICAM-1, and CD45 molecules. After enrichment and cultivation for approximately 3 days, these cells showed no adherent properties. The capacity of 4F7+ spleen dendritic cells to activate allogeneic T cells in the primary mixed lymphocyte reaction was similar to freshly isolated Ia+ Langerhans cells. With regard to the induction of a proliferative response of CD4+ naive T cells that were incubated with concanavalin A or anti-CD3 mAb, 4F7+ spleen dendritic cells were two to three times more potent than spleen microphages and B cells. Furthermore, 4F7+ cells efficiently stimulated the antigen dependent proliferation of a T helper cell line. The mAb 4F7 will be useful for the purification of dendritic cells and for functional and molecular biological studies.