thymosin and Dermatitis--Contact

The intraepithelial lymphocyte (IEL) network of T-cell receptor gammadelta+ (Vgamma5+) dendritic epidermal T cells (DETC) in murine skin down-regulates cutaneous inflammation, although the mechanism is unknown. Thymosin-beta4 (Tbeta4), identified by serial analysis of gene expression as a predominant transcript in gut IEL, encodes both a ubiquitous actin-binding protein (UTbeta4) with demonstrated capacity to inhibit neutrophilic infiltration, and a splice-variant limited to lymphoid tissue (LTbeta4) with unknown bioactivity. Freshly isolated Vgamma5+ DETCs expressed both forms, while only LTbeta4 was preferentially up-regulated after cellular activation in vitro. To compare the anti-inflammatory properties of LTbeta4 and UTbeta4 in the skin in vivo, the biological activities of synthesized polypeptides were assessed using three different strategies: neutrophil infiltration by footpad lambda-carrageenan injection; irritant contact dermatitis to 12-O-tetradecanoylphorbol 13-acetate; and allergic contact dermatitis to 2,4-dinitrofluorobenzene. These studies clearly showed that the anti-inflammatory activities of LTbeta4 were broader and most often stronger than those of UTbeta4. Thus, the activation-responsive expression of the lymph-specific form of Tbeta4 may be one mechanism by which DETC, and possibly other IELs, down-regulate local inflammation.

Topics: Alternative Splicing; Animals; Anti-Inflammatory Agents; Biological Assay; Cells, Cultured; Dendritic Cells; Dermatitis, Allergic Contact; Dermatitis, Contact; Dermatitis, Irritant; Female; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Microfilament Proteins; Receptors, Antigen, T-Cell, gamma-delta; Skin; Thymosin

The effect of selected compounds with known immunoregulatory activity was examined in a 45-h sensitization period oxazolone contact-sensitivity reaction. Oxazolone sensitivity was induced by applying 0.1 ml of 5% oxazolone in absolute ethanol to the shaved abdomen of C57Bl/6 mice on day 0. Challenge with oxazolone followed 45 h later and was accomplished by painting a 5% solution of oxazolone in absolute ethanol on the left hindpaw. The response at 24 h was determined plethysmographically. Histamine (0.062-1.0 mg/kg, subcutaneously, twice a day), concanavalin A (0.31-5.0 mg/kg intravenously), penicillamine (6.25-25 mg/kg, subcutaneously), chloroquine (6.25-25 mg/kg, subcutaneously), and thymosin fraction 5 (0.125-1.25 mg/kg subcutaneously) all stimulated the oxazolone reaction when administered on day 0. These data suggest that the low-grade oxazolone response may be a useful assay to detect immunostimulatory activity.

Topics: Adjuvants, Immunologic; Animals; Chloroquine; Dermatitis, Contact; Dose-Response Relationship, Drug; Histamine; Male; Mice; Mice, Inbred C57BL; Oxazolone; Penicillamine; Thymosin

Unresponsiveness was produced in mice by three feeds of high doses of oxazolone or picryl chloride. The mice were then sensitized and contact sensitivity assessed by ear swelling. Adult thymectomy prevented the unresponsiveness caused by feeding. In some but not all experiments adult thymectomy also increased the response to a single skin paint. This effect of thymectomy was apparent at 1 week and reached a plateau at 2-3 weeks. The effect of adult thymectomy, on unresponsiveness caused by feeding and its ability to increase the contact sensitivity skin reaction, was reversed by treatment with crude thymosin fraction V.

Topics: Animals; Dermatitis, Contact; Dose-Response Relationship, Drug; Immune Tolerance; Mice; Oxazolone; Picryl Chloride; Spleen; Thymectomy; Thymosin; Trinitrobenzenesulfonic Acid