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Biomedical subjects

U Tjernlund

Publications and source records attributed to U Tjernlund.

At least 19 recordsLinked to original sources

T-cell response to purified protein derivative after removal of Langerhans' cells from epidermal cell suspensions containing keratinocytes expressing class II transplantation antigens.

In a previous study we observed that human epidermal cell (EC) suspensions containing HLA-DR-expressing keratinocytes showed an amplified T-cell response to purified protein derivative (PPD). To evaluate further the possible immunological importance of class II transplantation antigens on keratinocytes we have compared the T-cell response to PPD in the presence of the following stimulator cells: EC suspensions from normal skin, or EC from tuberculin-reactive skin with or without removal of Langerhans' cells. The proliferation of purified T lymphocytes from peripheral blood in response to PPD in the presence of various concentrations of autologous EC was measured by [3H]thymidine incorporation on day 6. In 3 experiments out of 4 the EC from tuberculin-reactive skin, containing 28-76% HLA-DR-expressing cells as judged by immunocytochemistry (which also revealed fairly numerous HLA-DQ/-DP-expressing keratinocytes and a slight increase in CD36- and CD4- but not CD1-expressing cells), induced a more pronounced T-cell response to PPD than did normal EC. This was not the case in the fourth experiment, in which a small number of HLA-DR-(15%) and few if any HLA-DQ-/-DP-expressing keratinocytes were found. Immunomagnetic removal of CD1-reactive Langerhans' cells from the tuberculin-reactive EC suspensions resulted in a reduction of the T-cell response to PPD, in most cases down to background level (T cells alone + PPD). This study does not support the hypothesis that HLA-DR-expressing keratinocytes can in themselves act as antigen-presenting cells.

Adult

Low dosage alpha-interferon treatment in patients with advanced cutaneous T-cell lymphoma.

Treatment with high dose (10-50 x 10(6) IU/m2 three times a week) of alpha-interferon (alpha-IFN) has been shown to induce remissions in about 50% of patients with cutaneous T-cell lymphoma. The optimal alpha-IFN dose, however, is not known. 4 patients with advanced cutaneous T-cell lymphoma were therefore treated with alpha-IFN in low doses of 2-4 x 10(6) IU/m2 three times a wk. 1 complete, 1 partial and 1 minor remission were observed. Skin biopsies before and during treatment were taken from 2 of the patients and showed improvement. Low doses of alpha-IFN can thus induce remission in patients with cutaneous T-cell lymphoma.

Adult

A simple in vitro technique for studies on induction of class II transplantation antigens on keratinocytes.

A new technique is described for evaluation of the induction and kinetics of class II transplantation antigens on keratinocytes. By culturing small rat or human skin specimens for 2-5 days in media containing gamma-interferon, class II antigens were detected on keratinocytes by immunohistochemistry. This technique is rapid and technically simple compared to keratinocyte cultures and raises the possibility of studying other cells in the skin.

Animals

Amplification of T-cell response to PPD by epidermal cell suspensions containing HLA-DR-expressing keratinocytes.

The biological importance of the presence of class II transplantation antigens on highly differentiated epithelial cells such as keratinocytes in certain conditions, is still unknown. We have therefore investigated the antigen-presenting capacity of separated human epidermal cells obtained from tuberculin-reactive skin 6 days after intradermal injection of purified protein derivative (PPD). Earlier studies have shown a high percentage of HLA-DR-expressing keratinocytes at this time. Peripheral adherent blood cells were used as control stimulator cells and highly purified peripheral blood T lymphocytes as responder cells. The T-cell proliferation in response to PPD in the presence of autologous epidermal cells from normal and tuberculin-reactive skin was measured by [3H]thymidine incorporation on day 6. The latter cell population, 76-86% of which consisted of HLA-DR-expressing cells as judged by immunocytochemistry, induced a greater T-cell response to PPD than do normal epidermal cells. This discrepancy in the T-cell proliferation could not be explained by a difference in the numbers of anti-Leu 6 or anti-HLA-DQ-reactive Langerhans cells. The present data indicate that epidermal cell suspensions containing HLA-DR-expressing keratinocytes induce a greater T-cell response to PPD than do normal epidermal cells.

Adult

In vitro testing of contact sensitivity.

A new in vitro technique for the testing for contact sensitivity is described. The method is based upon the fact that in response to immunological stimuli, keratinocytes can start to synthesize and express class II histocompatibility antigens. Nickel sulphate (NiSO4) stimulated lymphocytes from nickel-sensitive persons, and the supernatant of these cells thus induced expression of HLA-DR on keratinocytes when co-cultured with autologous normal skin biopsies. This was in contrast to what was the case in healthy controls.

Dermatitis, Contact

Expression of HLA-DQ antigens on keratinocytes in Borrelia spirochete-induced skin lesions.

Skin biopsies were investigated with two different immunohistochemical techniques, thus revealing HLA-DQ antigens on HLA-DR-expressing keratinocytes in the late skin manifestations of a Borrelia spirochete infection. In the early skin lesions only HLA-DR antigens were present on the keratinocytes. The invariant gamma chain of class II transplantation antigens was observed on keratinocytes in 1:5 of the late cases. Upon penicillin treatment detectable HLA-DR and HLA-DQ antigens disappeared completely from the keratinocytes. Furthermore, the mononuclear cell infiltrates dominated by anti-Leu 1 and anti-Leu 3a-reactive cells and containing many cells with markers for activation (HLA-DR, HLA-DQ, transferrin, and interleukin 2 receptors) diminished markedly. The possibility that the expression of different class II transplantation antigens on keratinocytes might reflect separate functional demands of these cells or an altered immunological reactivity in the host, is discussed. The precise functional role of the temporary expression of the class II antigens on non-lymphoid cells, however, remains an enigma.

Acrodermatitis

Cell surface expression of invariant gamma-chain of class II histocompatibility antigens in human skin.

A rat monoclonal antibody (McAb 21:9) reactive with the human invariant gamma-chain of class II major histocompatibility complex (MHC)-encoded antigens was isolated and was shown to react with the carbohydrate-carrying, COOH-terminal part of the gamma-chain. The McAb 21:9 binds to a molecule that is identified as the gamma-chain for the following reasons: it has an apparent m.w. of 33,000, similar to that of the gamma-chain; it has a two-dimensional gel migration pattern identical to that of the gamma-chain; and it associates with immature, but not processed class II antigens. When used for immunohistochemical staining on sections of normal human skin, only dendritic, class II MHC antigen, and anti-Leu-6 reactive Langerhans cells are labeled in the epidermis. HLA-DR-expressing keratinocytes present in the tuberculin reaction, cutaneous T cell lymphoma, and lichen planus, however, did not react with the anti-gamma-chain antibody, nor with a HLA-DQ-reactive antibody. Cell surface expression of the gamma-chain was observed on 1 to 3% of normal viable epidermal cells in suspension. By using double indirect immunofluorescence, it was possible to demonstrate the simultaneous binding of anti-gamma-chain, anti-HLA-DR, anti-Leu-10, and anti-Leu-6 antibodies, respectively, on the same cells, thus confirming their identity as Langerhans cells. The presence of the gamma-chain on the surface of the immunocompetent Langerhans cells may indicate that the cell surface, not the cytoplasm as has been suggested, is the site of the primary function of the gamma-chain.

Adult

Distribution of interleukin-2 receptor bearing lymphocytes in the skin. A comparative study of allergic and irritant contact dermatitis, tuberculin reaction and cutaneous T cell lymphoma.

The tissue distribution of T cells and interleukin-2 receptor bearing (Tac+) lymphocytes was studied immunohistochemically in frozen sections of biopsies from inflamed skin. In skin lesions caused by irritant or immunologic stimuli, relatively few (less than 5%) of the total dermal infiltrating T cells were Tac+, but in both types of conditions the Tac+ cells showed a predeliction for the epidermis. In skin lesions from patients with cutaneous T cell lymphoma a relatively high proportion of dermal T lymphocytes were Tac+. Tac+ as well as Tac- T lymphocytes may thus migrate to a tissue secondary to several different stimuli. The demonstration of a non-random distribution of Tac+ lymphocytes in the non-malignant inflammatory conditions in the present study indicate that the epidermis may have a special role in the activation of T lymphocytes.

Antibodies, Monoclonal

Class II transplantation antigens in the late human skin tuberculin reaction.

The presence of class II transplantation antigens on keratinocytes and the phenotypes of the inflammatory cells in the late human skin tuberculin reaction were analysed with immunohistochemical double staining techniques in frozen sections of skin biopsies taken 10-45 days after intradermal purified protein derivative (PPD) injection. Dermal cell infiltrates decreased with time but were found throughout the observation period. Most of the cells in the perivascular infiltrates expressed HLA-DR antigens. Some of these cells are probably 'activated' macrophages, since they expressed OKM1 and OKT9 antigens in consecutive sections. Another less frequent cell population which reacted with RFD1 antibodies are presumably interdigitating cells. About half the perivascular cells were anti-Leu 3a-positive (T 'helper/inducer' phenotype). HLA-DR but not HLA-DQ antigens were detected on keratinocytes. This acquired expression of HLA-DR antigens on the epithelial cells disappeared between 17 and 30 days. If HLA-DR-expressing keratinocytes have immunoregulatory functions these might be different from those of other HLA-DR-expressing cell types that also express HLA-DQ molecules.

Epidermal Cells

T-cell subsets in multiple sclerosis: a comparative study between cell surface antigens and function.

Pokeweed mitogen (PWM)-driven immunoglobulin synthesis (IgG, IgA, IgM) and concanavalin A (Con A)-stimulated suppression of allogeneic mixed leukocyte reaction (MLR) were studied and compared to T-cell subsets defined by monoclonal antibodies OKT4 and OKT8 in patients with multiple sclerosis (MS). The group of patients with active progressive MS showed diminished suppressor activity as measured by T-cell functional tests and also an elevated OKT4/OKT8 ratio. The group of MS patients in remission did not show these abnormalities. However, this correlation between functional tests and T-cell phenotypes was not found when separate individuals were considered within the subgroups of MS. Since neither OKT4 nor OKT8-reactive cells represent homogeneous functional subsets of T cells, the OKT4/OKT8 ratio does not account for the functional immunological status of separate individuals but rather provides a global evaluation of T-cell subset disturbances in different groups of diseases.

Adult

Human keratinocytes express HLA-DR antigens in the tuberculin reaction.

The cellular response in the human skin tuberculin reaction was studied with immunohistochemical double-staining techniques in frozen sections of skin biopsies taken 6 h to 8 days after intradermal PPD injections. Cell infiltrates were observed from day 2 onwards and increased in size up to 4 days. Most of the infiltrating cells reacted with anti-Leu 3a (T 'helper/inducer' phenotype) antibodies. In contrast to normal epidermis, not only Langerhans cells but also keratinocytes expressed HLA-DR antigens from day 4 onwards. The induction of HLA-DR antigens on keratinocytes may be secondary to T-cell activation. Since the HLA-DR expression on keratinocytes appeared late in the tuberculin reaction, the function may be to suppress rather than enhance the immune response.

Adult

Linear IgA dermatosis: a study of ten adult patients.

Ten adult patients with homogeneous-linear deposition of IgA along the basement membrane zone have been studied. The direct immunofluorescence IgA pattern was stable, and there was no deposition of IgG or IgM. The clinical presentations were heterogeneous and resembled dermatitis herpetiformis (DH) (3 cases) or bullous pemphigoid (5 cases). Two patients had widespread gyrate blistering lesions of acute onset. Pruritus was constantly present. The course of the disease was chronic except for one patient who had a spontaneous remission after 5 years. The histology was indistinguishable from "classical" DH with granular IgA in dermal papillae. The patients studied in the present investigation did not show the high incidence of atrophic intestinal villi found in "classical" DH. Five of 9 cases carried the haplotype HLA-A1, B8, DR3. In spite of a close similarity between linear IgA dermatosis and DH, differences exist which indicate discrepancies in etiopathogenesis.

Adult

Antigenic similarities and differences in genus Pityrosporum.

Using the indirect immunofluorescence technique no differences were observed in intensity of staining when antisera against Pityrosporum orbiculare and P. ovale or IgG fractions of these were incubated with P. orbiculare and P. ovale cells. However, a weaker reaction was observed with these antisera and P. pachydermatis cells. With IgG fractions the nonspecific fluorescence was minimized. Fungal cells in biopsies from tinea versicolor lesions showed a brilliant staining with the IgG fractions of antisera against P. orbiculare. This investigation indicates a close antigenic relationship between all of the 3 Pityrosporum species. A common antigenicity was found between P. orbiculare and P. ovale cells as well as between P. orbiculare cells from culture and the fungal cells in biopsies from tinea versicolor lesions. This strongly suggests that these 2 species are identical with each other and with the organism found in tissue.

Animals