Biomedical subjects

J C Prinz

Publications and source records attributed to J C Prinz.

27 records · Page 2Linked to original sources

PubMed1994

T cell clones from psoriasis skin lesions can promote keratinocyte proliferation in vitro via secreted products.

Psoriasis vulgaris has been recognized lately as an immunologically mediated inflammatory skin disease. To analyze the pathogenetic role of T lymphocytes in the generation of psoriatic skin lesions, 105 T cell clones (TCC) and 10 T cell lines (TCL) were differentially isolated from dermis and epidermis of psoriatic skin specimens. Supernatants prepared from these T cells were studied for their effects on keratinocyte proliferation in vitro. Conditioned media from 14 of 77 epidermal TCC, 7 of which were CD8+, and from 8 of 28 dermal TCC, 5 of which were CD8+, reproducibly enhanced keratinocyte proliferation, with more pronounced mitogenic activities found in dermal TCC. Another 9 epidermal and 3 dermal TCC did not affect keratinocyte growth and supernatants from the remaining clones, as well as from the 5 epidermal and 5 dermal TCL, inhibited keratinocyte replication to varying degrees. Both mitogenic and suppressive activities were largely abolished by addition of an antiserum to interferon-gamma (IFN-gamma), while addition of epidermal growth factor or irradiated psoriatic TCL had little effect on the activities of the supernatants. These studies reveal that a subpopulation of lesional psoriatic T lymphocytes is capable of enhancing keratinocyte proliferation in vitro via secreted products. Their mitogenic capacity most likely requires IFN-gamma, but the ultimate effect is apparently determined by the presence of additional cytokines. Activation of T cells secreting such combinations of factors in vivo may contribute to the keratinocyte alterations characteristic of psoriatic skin lesions.

Cell Division↗

PubMed1994

T lymphocytes derived from skin lesions of patients with psoriasis vulgaris express a novel cytokine pattern that is distinct from that of T helper type 1 and T helper type 2 cells.

In various immunological disorders the pathomechanisms of tissue damage are causally associated with specific patterns of locally produced cytokines. To study the molecular and cellular mechanisms involved in the manifestation of psoriasis vulgaris we have assessed the cytokine mRNA profile expressed in lesional psoriatic skin and in T cell clones (TCC) that were established from skin lesions of patients with psoriasis. As demonstrated by use of the polymerase chain reaction (PCR), psoriasis lesions consistently exhibit transcription of a complex pattern of cytokines. It includes mediators selectively produced by T lymphocytes [interferon (IFN)-gamma, tumor necrosis factor (TNF)-beta, interleukin (IL)-2, IL-3 and IL-5] as well as cytokines secreted by various cell types [transforming growth factor (TGF)-alpha/-beta, TNF-alpha, IL-6/-8 and granulocyte-macrophage-colony stimulating factor], while IL-4 is missing. With the exception of TGF-alpha, this cytokine profile was also observed in lesional psoriatic T cell clones yielding supernatants mitogenic for keratinocytes in vitro (MTCC), but not in T cell clones yielding supernatants that inhibited keratinocyte proliferation (STCC). The congruent cytokine expression of psoriatic skin lesions and MTCC emphasizes that inflammation in psoriasis is driven by a sofar unrecognized regulatory T cell subset that may serve to control epidermal regeneration and convey immunosurveillance over epithelial surfaces. It is characterized by the combined expression of IFN-gamma, TGF-beta, IL-2 and IL-5 in the absence of IL-4 and by its selective capacity to enhance keratinocyte proliferation. This newly defined combination of regulatory properties of a distinct T cell population cannot be reconciled with an immune response of the T helper cells (TH)0, TH1 or TH2 type.

Base Sequence↗

PubMed1990

Expression of the Fc-receptor for IgE (Fc epsilon RII, CD23) on alveolar macrophages in extrinsic allergic alveolitis.

Expression of the Fc receptor for IgE (Fc epsilon R) was analyzed on alveolar macrophages (AM) in 10 patients with extrinsic allergic alveolitis (EAA) compared with 10 patients with sarcoidosis and to 6 apparently healthy controls. By using the anti-Fc epsilon RII mAb M-L25 in immunocytochemistry experiments, we found that greater than 60% of AM in 10 of 10 patients with EAA were strongly positive, as evidenced by visual analysis in light microscopy and by cytometry. By contrast, no significant staining was detected in sarcoidosis or in controls with either method. Similar results were obtained when Fc epsilon R were identified with preformed immune complexes consisting of NIP-specific human/mouse chimeric IgE antibody plus NIP-ovalbumin. Furthermore, greater than 60% of AM in patients with EAA stained positive for IgE, demonstrating that endogenous IgE is bound to the AM. Our data suggest that IgE antibodies bound to Fc epsilon RII on AM may be involved in pathophysiology of extrinsic allergic alveolitis by activation of the AM after binding of allergen to the cell surface IgE. Furthermore, with the clearcut pattern of Fc epsilon RII expression in extrinsic allergic alveolitis it may be possible to use CD23 antibodies for differential diagnosis of inflammatory lung disease.

Adult↗

PubMed1990

Allergen-directed expression of Fc receptors for IgE (CD23) on human T lymphocytes is modulated by interleukin 4 and interferon-gamma.

T lymphocytes bearing Fc receptors (FcR) for immunoglobulins are known to have immunoglobulin class-specific regulatory functions. Here we report that expression on T cells of the low-affinity FcR for IgE (Fc epsilon RII/CD23) is preferentially induced by stimulation with antigens that cause an IgE response. T cells from eight patients allergic to the hemoglobin of Chironomus thummi thummi mosquito larvae (CHIT I) were analyzed for reactivity with the anti-FcERII/CD23 monoclonal antibody (mAb) M-L25 under various conditions. No Fc epsilon RII/CD23+ T cells were observed among freshly isolated, resting peripheral blood mononuclear cells (PBMC). Stimulation of PBMC with CHIT I, however, induced a marked although transient Fc epsilon RII/CD23 expression on a large portion of the allergen-activated T lymphocytes. It reached a maximum of 37.2 +/- 4.6% Fc epsilon RII/CD23+ T cell blasts on day 5 of culture. The selectivity of this expression became evident when compared to non-allergenic control antigens: after stimulation of PBMC with tetanus toxoid or purified protein derivative from tuberculin a maximum of 4.6% +/- 1.4% and 4.2% +/- 1.1% T cell blasts was found to express Fc epsilon RII/CD23, respectively. Activation by an anti-CD3 mAb was insufficient to induce Fc epsilon RII/CD23 on T cells. The allergen-stimulated Fc epsilon RII/CD23+ T cells exclusively belonged to the CD4+CD29+ helper inducer T cell subset. Using a cDNA probe coding for the B cell Fc epsilon RII/CD23, Northern blot analysis revealed a 1.7-kb Fc epsilon RII/CD23 mRNA in extracts of highly purified allergen-stimulated T cells. It was of the same size as Fc epsilon RII/CD23 mRNA of the lymphoblastoid B cell line WI-L2. Of several cytokines tested [interleukin (IL) 1 to IL 6, interferon-gamma (IFN-gamma), tumor necrosis factor-alpha] only IL 4 and IFN-gamma significantly modified allergen-induced Fc epsilon RII/CD23 expression on T cells. The latter was enhanced nearly twofold in the presence of IL 4, and was almost completely abrogated by IFN-gamma. IL 4, however, could not increase the number of Fc epsilon RII/CD23+ T lymphocytes either alone or in combination with an anti-CD3 mAb. Taken together, the selective induction of Fc epsilon RII/CD23 on T cells by allergen and its inclusion in the regulatory network of cytokines point to an important role of Fc epsilon RII/CD23+ T lymphocytes in the human IgE response.

Allergens↗

PubMed1990

IgE-dependent antigen focusing by human B lymphocytes is mediated by the low-affinity receptor for IgE.

In this study we investigated the role of the low-affinity receptor for IgE (Fc epsilon RII, CD23) on Epstein-Barr virus (EBV)-transformed human B cells in the uptake and presentation to T cells of antigen after complexing with IgE. Cloned EBV-transformed B cells were incubated for 5 h with (4-hydroxy-3-iodo-5-nitrophenyl)acetyl (NIP)-haptenized tetanus toxoid (NIP-TT) or NIP-TT complexed with a chimeric human IgE/mouse anti-NIP monoclonal antibody (IgE x NIP-TT) and then contacted for 2 min with autologous cloned TT-specific T cells. Intracellular Ca2+ mobilization in T cells was determined as an early indicator of T cell activation. The antigen-presenting capacity of B cells was significantly increased by complexing the antigen with IgE. This effect could be selectively reversed in a dose-dependent manner by blocking the Fc epsilon RII with an anti-CD23 monoclonal antibody. The IgE-mediated increased capacity for presenting antigen became particularly evident when B cells were incubated with NIP-TT or IgE x NIP-TT for only 1 h at 4 degrees C, washed and then cultivated for 6 h at 37 degrees C allowing uptake and processing of the antigen. These results indicate a new role of the Fc epsilon RII/CD23 molecules in the uptake of antigen by APC which might be of importance in the maintenance of an ongoing immune response against allergens.

Antigen-Presenting Cells↗

PubMed1989

Induction of Fc epsilon R2/CD23 on human epidermal Langerhans cells by human recombinant interleukin 4 and gamma interferon.

Human rIL-4 and human rIFN-gamma are able to induce the expression of the low affinity receptor for IgE (Fc epsilon R2/CD23) on normal human epidermal Langerhans cells, whereas IL-2 and PMA have no effect. A synergistic effect is observed when both cytokines are combined. These receptors are synthesized de novo by the LC since cycloheximide completely inhibits the appearance of Fc epsilon R2/CD23. Fc epsilon R2/CD23+ LC may have a major role in the pathogenesis of atopic eczema, as well as in the regulation of IgE synthesis.

Antibodies, Monoclonal↗

PubMed1989

Occurrence of IgE-bearing epidermal Langerhans cells in atopic eczema: a study of the time course of the lesions and with regard to the IgE serum level.

Uninvolved and lesional skin of untreated and treated patients with atopic eczema has been investigated immunohistochemically to determine the conditions in which IgE-bearing CD1a+ Langerhans cells/indeterminate cells (LC/IC) occur in this disease. IgE-bearing epidermal dendritic cells were present in patients with elevated IgE serum level (greater than 300 UI/ml) and the staining pattern was stronger in lesional skin. On double immunostaining, a subpopulation of CD1a+ LC/IC was found not to bear IgE molecules as determined by the ratio IgE+/CD1a+ cells on serial sections as well. The ratio IgE+/CD1a+ cells decreased in patients who underwent a local therapy with glucocorticosteroids. These results suggest that the expression of IgE receptors and/or binding of IgE molecules on epidermal LC/IC in atopic eczema may be controlled by a complex network of mediators from the epidermis or the inflammatory infiltrate, or both, and that this phenomenon could be down regulated by glucocorticosteroids.

Antigens, CD1↗

PubMed1987

Expression of Fc epsilon receptors on activated human T lymphocytes.

Our results clearly demonstrate that the low-affinity receptor for IgE (Fc epsilon R) is an activation antigen transiently expressed on a subpopulation of human T lymphocytes. It can be selectively induced by stimulation with certain antigens or lectins, but it is not found on resting T cells. The increased numbers of activated Fc epsilon R+ T cells observed after stimulation of peripheral blood mononuclear cells (PBMC) from bee venom allergic patients with the specific allergen phospholipase A2 (PLA2) suggest that Fc epsilon R+ T cells might very well be involved in the regulation of the human IgE response against the respective antigen. These results were obtained by the use of two monoclonal antibodies, M-L25 and M-L47, which were raised against the human low-affinity Fc epsilon R in our laboratory. After stimulation of PBMC with phytohemagglutinin a peak of 7.6 +/- 6% Fc epsilon R+ T cells was observed on day 3, with pokeweed mitogen of 0.8 +/- 0.8% on days 2 and 3, and with concanavalin A of 0.6 +/- 0.7% Fc epsilon R+ T cells on day 2. Stimulation of PBMC with tetanus toxoid (TT) induced Fc epsilon R on maximally 0.6 +/- 0.8% of the total T cells (day 4), stimulation with purified protein derivative from tuberculin (PPD) on 0.2 +/- 0.6% of the T cells (day 2). In contrast to these antigens, stimulation of PBMC from bee venom allergic patients with PLA2 induced as a peak 2.5 +/- 2.5% of the total T cells to express Fc epsilon R (day 5), although the stimulated T cell population was much smaller than with TT or PPD, as was shown by their stimulation indices. The allergen-stimulated Fc epsilon R+ T cells were exclusively T4+. The Fc epsilon R-expression index was determined, which for a specific antigen or lectin correlates the percentage of Fc epsilon R+ T cells to the stimulated T cell population, respectively.

Allergens↗

PubMed1987

Fc-receptors for IgE on human lymphocytes. Detection with a rosetting assay using a recombinant human/mouse IgE antibody and characterization with monoclonal antibodies.

Two monoclonal antibodies, M-L25 and M-L47, were produced against the human lymphoid Fc receptor for IgE (Fc epsilon R). These antibodies were identified by their ability to selectively inhibit the binding of IgE to Fc epsilon R+ lymphoid cells as demonstrated by a newly developed IgE rosetting assay. In this method, NIP coated ox erythrocytes were complexed with a NP-specific recombinant chimeric human/mouse IgE antibody and employed as indicator cells for the detection of Fc epsilon R+ cells. The anti-Fc epsilon R antibodies stained 4.6 +/- 2.3% of normal peripheral blood mononuclear cells, 0.4 +/- 0.3% of T cells, 22.2 +/- 11.7% of the non-T cell fraction, and 34.9 +/- 2.9% of tonsil cells. Less than 0.1% of monocytes, basophilic and eosinophilic granulocytes, platelets, and thymus cells were labelled. This indicates an antigenic heterogeneity of the low affinity Fc epsilon R on lymphocytes and the Fc epsilon R found on monocytes, platelets, and eosinophilic granulocytes. The lymphoid Fc epsilon R was immunoprecipitated by M-L25 from the lysate of surface iodinated lymphoid cells. Three polypeptide chains were identified having an apparent MW of 40, 82, and 100 kd under non-reducing, and of 42, 115, and 145 kd under reducing conditions, suggesting a multichain structure of the human lymphoid Fc epsilon R.

Antibodies, Monoclonal↗