Langerhans cells in the development of skin cancer: a qualitative and quantitative comparison of cell markers in normal, acanthotic and neoplastic ovine skin.

The distribution of Langerhans cells in normal, acanthotic and neoplastic ovine epithelium was examined using the enzyme marker Acetylcholinesterase (AchE) and monoclonal antibodies (MoAb) to CD1 (20.27) and MHC Class II (49.1 and 28.1) molecules. In normal skin, where Langerhans cells were regularly spaced within the basal layer, qualitative observations and direct pairwise testing showed that AChE was superior to the MoAb in detecting these cells. Significantly more (P < 0.01) dendritic cells were also detected with MoAb 49.1 than MoAb 20.27 or 28.1, suggesting differential expression of MHC Class II subsets and the presence of CD1- MHC Class II+ granule- dendritic cells in sheep analogous to indeterminate cells of man. In acanthotic skin, compared to normal skin, Langerhans cells were less numerous, irregular and more suprabasal in distribution and their morphology was occasionally swollen and indistinct. No difference was seen in the ability of AChE and MoAb in detecting Langerhans cells, however pairwise testing of markers did demonstrate that significantly more (P < 0.05) cells without dendritic processes were stained with MoAb 49.1 than with 20.27 or 28.1. In all squamous cell carcinomas examined dendritic cells that stained for AChE, CD1 or MHC Class II antigens were concentrated at the peripheral areas of neoplastic epithelium. Many dendritic cells were detected with MoAb to MHC Class II antigens, whereas CD1 and AChE positive dendritic cells were rare in tumor bearing tissue. The quantitative differences in the immunohistochemical staining of Langerhans cells between normal, acanthotic and neoplastic epithelium were consistent with ultrastructural studies. When compared with those of a newborn lamb, which had had very little exposure to antigens or ultraviolet radiation (UVR), the Langerhans cells of the aged sheep were deformed and contained far fewer Birbeck granules. The abnormalities were progressively more severe in acanthotic and neoplastic skin. These observed changes may have resulted from UVR induced damage and may be indicative of impaired function involved in the development of skin cancer.

Major histocompatibility complex antigens in normal, acanthotic and neoplastic ovine skin: an association been tumor invasiveness and low level MHC class I expression.

The distribution and density of ovine MHC class I and class II antigens in normal, acanthotic and malignantly transformed ovine skin was investigated using monoclonal antibodies and an immunoperoxidase technique. The subjects were sheep that had been exposed to high levels of sunlight for more than 6 years. The expression of MHC class II antigens in the plasma membrane of cells within the normal epidermis was restricted to basally located dendritic and mononuclear cells. Normal keratinocytes did not express MHC class II antigens. However, we observed low levels of intracellular MHC class II expression in both acanthotic and neoplastic keratinocytes. Expression of MHC class I antigens was variable in normal and acanthotic epithelium; it was usually present, but of low intensity in very early ovine squamous cell carcinoma and was increased in small, but morphologically typical, tumors. Tumors originating on the nose, which are more invasive than those on the ear, were found to express significantly less MHC class I (P < 0.05). Thus, an association between tumor invasiveness and low level expression of MHC class I was apparent. This may have diagnostic value and highlights a mechanism by which neoplastic cells may evade immune surveillance by T cells.

The distribution of lymphocyte subpopulations in normal and acanthotic ovine skin.

The prevalence and distribution of lymphocyte subpopulations in normal and acanthotic ovine skin were investigated using monoclonal antibody immunocytochemistry. CD8+ cells were predominant in the epidermis of both normal and acanthotic skin, but were CD8+ cells, CD4+ cells and T19+ cells infrequent in normal epidermis. Within the dermis of normal skin, there were significantly greater numbers of CD4+ and T19+ cells situated around the superficial dermal vessels than in any other region examined. The majority of the CD8+ cells adjoined vessels, but the proportion that did not was greater for CD8+ than for CD4+ or T19+ cells. The CD4+ and CD8+ subsets were represented equally in adnexa. T cells were of memory phenotype. B cells and naive T cells, both of which express the CD45RA antigen, were rarely seen and tended to be associated with vessels in both normal and acanthotic skin. None of the T19+ cells (which are gamma delta+) resembled the dendritic gamma delta cells seen in murine epidermis. Acanthotic skin was strikingly different to normal skin. There was a greater abundance of T cells, particularly CD4+ cells, in acanthotic epidermis and the numbers of CD8+ and T19+ cells, and to a greater extent CD4+ cells, were greater at the dermal-epidermal junction. There were more CD4+ and CD8+ cells in the superficial dermal stroma of acanthotic skin. Within the dermis of acanthotic skin, T cells were concentrated near vessels but the apportioning of T cells between stromal/adnexal and vessel-associated sites differed from normal. Such observations suggest that migration away from perivascular sites and into the stroma may be controlled separately for subregions of skin and for each T cell subset. The role of this altered nonrandom migration of T cells in skin chronically exposed to ultra violet radiation is uncertain.

The relationship between the prevalence of uterine lesions and the use of medroxyprogesterone acetate for canine population control.

The prevalence of uterine disease was established during desexing of 175 bitches in the Torres Strait and Cape York, 42 of which had been treated with injectable medroxyprogesterone acetate (MPA) for oestrus postponement. The prevalence of uterine lesions was 45% for treated bitches, 5% for untreated bitches, and 14.9% for the sample population. A highly significant relationship (P < 0.01) between MPA treatment and uterine lesions was established. A significant association (P < 0.05) between age (> 2 years old) and uterine lesions was found, most likely attributable to a significantly higher proportion (P < 0.01) of MPA-treated bitches in the older population. There was no significant difference in the effect of MPA on the prevalence of uterine lesions between older and younger bitches. There was no effect of parity on the prevalence of uterine lesions.