Type IV allergy to natural hirudin confirmed by in vitro stimulation with recombinant hirudin.
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Antithrombins↗
Biomedical subjects
T M Zollner
Publications and source records attributed to T M Zollner.
T-cell-receptor repertoire in chronic plaque-stage psoriasis is restricted and lacks enrichment of superantigen-associated V beta regions.
Preferential usage of certain T-cell receptors by the lymphocytic infiltrate in psoriasis might indicate the involvement of an antigen in the pathogenesis of this disease. However, to date there are no data on the complete T-cell-receptor V alpha and V beta repertoire in psoriatic patients. We therefore compared the usage of T-cell-receptor variable regions in blood and skin of 10 patients with chronic plaque-stage psoriasis by means of semiquantitative polymerase chain reaction. Additionally, HLA class II alleles were analyzed by means of sequence-specific oligonucleotide typing. A considerable restriction of the T-cell-receptor repertoire was observed in the skin, where up to 20% of the variable regions present in the blood were not detectable. This was true for both alpha- and beta-chains. However, no interindividually constant pattern of T-cell-receptor restriction was deducible. Inconsistently, a certain preferential usage of some beta chains occurred within the cutaneous compartment. This report on the complete T-cell-receptor V alpha and V beta repertoire in psoriasis documents the restricted receptor repertoire of infiltrating T cells and a lack of enrichment of superantigen-associated V beta regions. Thus superantigens seem not to play a pathogenetically relevant role in chronic plaque-stage psoriasis.
Genetic Heterogeneity↗
Differential expression of heat shock protein 70 (HSP70) and heat shock cognate protein 70 (HSC70) in human epidermis.
Autoimmunity and microbial agents have been suggested as playing a pathogenetic role in psoriasis. Since immune responses to microbial infections are often directed towards heat shock proteins (HSP), we investigated the expression of three HSP families in normal and inflamed human skin. Specimens from ten patients with psoriasis and three patients with positive patch tests for nickel and from five healthy volunteers were analysed by means of immunohistochemistry. The patterns observed were qualitatively similar in these conditions showing only minor quantitative differences. Psoriatic epidermis exhibited the highest level of expression. HSP27, HSP70 and heat shock cognate protein 70 (HSC70) were readily detectable. HSP27 was homogeneously distributed throughout the epidermis, whereas HSP70 was restricted to the basal layer and HSC70 primarily to the suprabasal layers. Other HSPs were detected to a lesser degree and showed a more irregular pattern. Thus, the qualitative expression pattern of HSPs seems to be constant between different skin conditions, but the expression of constitutive and inducible HSP70 depends on the differentiation state of keratinocytes.
Blotting, Western↗
Enhancement of MHC-unrestricted cytotoxic activity of human CD56+ CD3- natural killer (NK) cells and CD3+ T cells by rhamnogalacturonan: target cell specificity and activity against NK-insensitive targets.
Rhamnogalacturonan-mediated enhancement of MHC-unrestricted cytotoxicity was studied with freshly isolated CD56+CD3- natural killer (NK) cells, interleukin-2 (IL-2)-activated CD56+ lymphokine-activated killer (LAK) cells und IL-2/anti-CD3-activated T cells as effector cells using NK-sensitive and NK-insensitive tumor cells as targets. The rhamnogalacturonan fractions IM, IP, and IQ were prepared from commercially available extracts of Viscum album. The dose/response relation of IM, IP, and IQ demonstrated the presence of various concentrations of cytotoxicity-enhancing compounds in all three fractions that were identified as rhamnogalacturonans by degradation studies with poly-alpha-D-galacturonidase (EC 3.2.1.15) and alpha-1,6-rhamnosidase (EC 3.2.1.40). Specific cytotoxicity of all three effector cell populations as well as the respective rhamnoagalacturonan-mediated cytotoxicity enhancement was readily inhibited in a dose-dependent manner by 60%-deacetylated mannose pentaacetate. Rhamnogalacturonan-mediated enhancement of cytotoxicity of fresh CD56+ NK cells was also observed with four of five NK-insensitive tumor cells as targets, indicating that the effector-cell/tumor-cell bridging activity of rhamnogalacturonans renders NK-insensitive targets susceptible to NK-mediated lysis. Moreover, the rhamnogalacturonan-mediated cytotoxicity enhancement became even more prominent when lymphokine-activated CD56+ LAK and CD3+ T cells were assayed with the NK-insensitive tumor cell targets.
Antigens, CD↗
Predominant usage of distinct T-cell receptor V beta regions by epidermotropic T cells in psoriasis.
To investigate the role of T cells in psoriasis, we analyzed the T-cell receptor (TCR) repertoire in peripheral blood lymphocytes (PBLs) and in skin lesions of 9 patients with chronic plaque-stage psoriasis by means of immunohistochemistry. An extended panel of monoclonal antibodies detecting 11 different V beta families was employed in this study. In the peripheral blood, no predominant TCR V beta expression was detected and interindividual differences were small. Skin-infiltrating T cells showed only marginal differences in the TCR V beta usage when compared with PBLs. However, in 3 patients the intraepidermal infiltrate comprised up to 40% of T cells expressing a TCR V beta region which was virtually absent in the peripheral blood and the dermal infiltrate. Thus, although the TCR V beta usage of skin-infiltrating T cells showed little difference compared to PBLs, several cases exhibited a significant increase of epidermotrophic T cells using one particular V beta region.
Epidermis↗
Activation of human monocyte/macrophage cytotoxicity by IL-2/IFN gamma is linked to increased expression of an antitumor receptor with specificity for acetylated mannose.
Spontaneous cytotoxicity of human monocytes (purity: 92-95%) against K562 tumor cells was only observed in 31% healthy donors but, in the presence of rhamnogalacturonan (500 ng/ml), enhanced cytotoxicity was recorded for 79% (n = 14) of the donors. Monocytes activated by culturing with interleukin-2 and/or IFN gamma showed increased antitumor cytotoxicity against K562 tumor cells in 86% (n = 21) of the donors exhibiting additional increases in specific cytotoxicity when the cytotoxicity assays were carried out in the presence of rhamnogalacturonan. Increases of monocyte cytotoxicity achieved by activation with cytokines coincided with increased formation of monocyte/tumor cell conjugates. Similarly, increased monocyte cytotoxicity mediated by rhamnogalacturonan also correlated with increased monocyte/tumor cell conjugate formation most likely due to effector cell/target cell bridging as was originally described for rhamnogalacturonan interacting with CD56+ natural killer or lymphokine-activated killer cells and tumor cells. The chemospecificity of the monocyte-based receptors responsible for cytotoxicity and for monocyte/tumor cell conjugate formation, as well as for their rhamnogalacturonan-mediated enhancements, appears to be identical since all these effects could be inhibited in a dose-dependent manner by partially deacetylated (60%) mannose pentaacetate.
Cytotoxicity, Immunologic↗
Mycetoma due to Exophiala jeanselmei and Mycobacterium chelonae in a 73-year-old man with idiopathic CD4+ T lymphocytopenia.
Exophiala jeanselmei and Mycobacterium chelonae were isolated from cutaneous nodules in a 73-year-old man with mycetoma of the right lower leg. Further evaluation revealed CD4+ lymphocytopenia without evidence of HIV infection. Antibodies to HIV 1/2, p24 antigen and HIV 1/2 (PCR) and reverse transcriptase activity were not detectable. The patient was not a member of any HIV risk group. He had not previously undergone therapy or suffered from immunodeficiency. This case clearly demonstrates that infections with opportunistic moulds and/or atypical mycobacteria should be taken into consideration not only in patients with classical immundeficiency diseases but also in apparently healthy patients because infection with these agents can be the first sign of underlying immunodeficiency.
Aged↗
Induction of NK-like activity in T cells by IL-2/anti-CD3 is linked to expression of a new antitumour receptor with specificity for acetylated mannose.
The generation of MHC-unrestricted cytotoxicity of highly enriched human CD3+ T cells (95-99%) by treatment with IL-2 and/or anti-CD3 antibodies was studied. T cells obtained by positive immunomagnetic sorting (anti-CD3) developed comparable specific cytotoxicities against K562 and Daudi cells when cultured with IL-2 and anti-CD3 for 96 h (80% of donors; n = 25). This increase of MHC-unrestricted cytotoxicity correlated fairly well with an increased formation of T cell/tumour cell conjugates. Moreover, simultaneous expression of a rhamnogalacturonan-binding receptor on activated T cells could be demonstrated. Rhamnogalacturonan was reported to enhance cytotoxicity of CD56+ NK cells by effector cell/target cell bridging. Untreated CD3+ cells hardly reacted with rhamnogalacturonan and IL-2-activated T cells showed only a moderate enhancement of cytotoxicity in the presence of rhamnogalacturonan. However, when CD3+ T cells had interacted with anti-CD3 antibodies during cell-sorting or during subsequent culturing with IL-2, enhancement in cytotoxicity and increased formation of lytic effector cell/tumour cell conjugates in the presence of rhamnogalacturonan could be readily demonstrated, indicating a bridging effect analogous to CD56+ NK cells. The conjugate formation of activated T cells with tumour cells as well as the additional rhamnogalacturonan-mediated bridging must be based on the expression of receptors with acetyl mannose specificity, since enhancements of MHC-unrestricted T cell cytotoxicity and conjugate formation were inhibited in a dose-dependent manner when acetylated mannose was present in the assays.
Antibodies, Monoclonal↗