Biomedical subjects

S Grabbe

Publications and source records attributed to S Grabbe.

98 records · Page 6Linked to original sources

PubMed1993

Regulation of Langerhans cell function by nerves containing calcitonin gene-related peptide.

Several observations suggest interactions between the immune and nervous systems. Psoriasis and atopic dermatitis may worsen with anxiety and have been associated with anomalous neuropeptide regulation. Neurotransmitters affect lymphocyte function and lymphoid organs are innervated. Calcitonin gene-related peptide (CGRP) is a neuropeptide and vasodilator that modulates some macrophage functions, including antigen presentation in vitro. CGRP is associated with Langerhans cells (LC) in oesophageal mucosa, particularly during inflammation, is present in epidermal nerves and is associated with Merkel cells. We examined the ability of CGRP to modulate LC antigen-presenting function and asked if CGRP-containing nerves impinge on LC. We report here that CGRP-containing nerve fibres are intimately associated with LC in human epidermis and CGRP is found at the surface of some LC. In three functional assays CGRP inhibited LC antigen presentation. These findings indicate that CGRP may have immunomodulatory effects in vivo and suggest a locus of interaction between the nervous system and immunological function.

Adult↗

PubMed1993

[Metastasizing eccrine porocarcinoma].

We report on an 84-year-old female patient who presented with abundant firm skin nodules and massive lymphoedema restricted to the left leg. Metastasizing eccrine porocarcinoma was diagnosed by the unusual circumscribed pattern of the cutaneous metastases and the histological detection of intraepidermal and intradermal PAS-positive tumour cells. This diagnosis was established by the histopathological reexamination of a small skin tumour on the left ankle, which had been misinterpreted as actinic keratosis 5 years before. The initiated local radiation therapy with fast neurons and cobalt-60 resulted in partial regression of the cutaneous metastases and lymphoedema, but was not able to hamper the fatal outcome directly resulting from tumour cachexia.

Aged↗

PubMed1992

Tumor antigen presentation by epidermal antigen-presenting cells in the mouse: modulation by granulocyte-macrophage colony-stimulating factor, tumor necrosis factor alpha, and ultraviolet radiation.

I-A+ epidermal antigen-presenting cells (APCs, Langerhans cells) have been shown to present tumor-associated antigens (TAAs) and to induce tumor immunity in vivo. This study examined the effects of ultraviolet radiation (UVR) and the cytokines granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor alpha (TNF-alpha) on the ability of epidermal cells (ECs) to induce or to elicit immunity against the murine spindle cell tumor S1509a. Naive syngeneic mice were immunized three times at weekly intervals with ECs that had been cultured in GM-CSF for 18 h and then pulsed with TAA derived from S1509a. This resulted in protective immunity against subsequent tumor challenge, providing a model to study the conditions required for sensitization against TAAs by epidermal APCs. Culture of ECs in GM-CSF was required for induction of significant protective tumor immunity, and UV irradiation or incubation in TNF-alpha for 2 h after GM-CSF incubation abrogated the immunostimulatory effect of GM-CSF. However, unlike UVR, TNF-alpha did not significantly inhibit the induction of immunity when ECs were exposed to TNF-alpha before overnight incubation in GM-CSF, together with GM-CSF, or after pulsing with TAA, and anti-TNF-alpha antibody treatment did not abrogate the effects of UVR on this system. Furthermore, TNF-alpha incubation of ECs augmented their ability to elicit delayed-type hypersensitivity (DTH) and also enhanced elicitation of DTH by GM-CSF-cultured ECs, whereas UV-irradiation reduced it in a dose-dependent fashion. Taken together, these results demonstrate that GM-CSF, TNF-alpha, and UVR are significant regulators of tumor antigen presentation by epidermal APCs and that the effects of the cytokines examined differ with regard to induction or elicitation of immunity.

Animals↗

PubMed1992

Cyclosporin increases granulocyte/macrophage colony-stimulating factor (GM-CSF) activity and gene expression in murine keratinocytes.

Keratinocytes produce multiple cytokines in response to a variety of stimuli. The release of interleukin 1 (IL-1) from keratinocytes may be significant in initiation of cutaneous inflammation, and the presence of granulocyte/macrophage colony-stimulating factor (GM-CSF) is thought to be important in the regulation of antigen-presenting function by epidermal Langerhans cells. Because cyclosporin inhibits interleukin 2 release from T cells, it has been suggested that cyclosporin may function as an anti-inflammatory agent within the epidermis through inhibition of keratinocyte cytokine release. This investigation examined the direct effect of cyclosporin on the production of GM-CSF by murine keratinocytes and the keratinocyte cell line PAM 212. GM-CSF bioactivity increased in cell supernatants from keratinocytes exposed in vitro to 1 microgram/ml cyclosporin for up to 24 h. GM-CSF and IL-1 mRNA levels in keratinocytes cultured under similar conditions or in the presence of lipopolysaccharide also increased. The lack of inhibition of GM-CSF expression following cyclosporin treatment is consistent with recent observations in T cells and is opposite to the effect of cyclosporin on interleukin 2.

Animals↗

PubMed1992

Effects of immunomodulatory cytokines on the presentation of tumor-associated antigens by epidermal Langerhans cells.

The recognition and presentation of tumor-associated antigens by cutaneous antigen-presenting cells (APC) may play an important role in the establishment of effective defense mechanisms against newly emerging tumors in the skin. Recent data demonstrate the ability of I-A+ epidermal cells (Langerhans cells) to present tumor-associated antigens for the induction of protective tumor immunity and elicitation of delayed-type hypersensitivity against the murine spindle cell tumor, S1509a. Furthermore, the local cytokine microenvironment in the vicinity of a cutaneous neoplasm may regulate the ability of resident epidermal APC to initiate and/or to elicit protective immunity against incipient cutaneous neoplasms. This article summarizes the effects of granulocyte-macrophage/colony-stimulating factor (GM-CSF), interleukin-1 alpha (IL-1 alpha), tumor necrosis factor-alpha (TNF alpha), transforming growth factor-beta (TGF beta), and interferon-gamma (IFN gamma) on the modulation of antigen presentation by epidermal APC. Our data indicate that these cytokines significantly and differentially modify the ability of epidermal cells to present tumor-associated antigens and that their effects differ with regard to induction of primary immunity (sensitization) or elicitation of secondary immune responses.

Adjuvants, Immunologic↗

PubMed1991

Tumor antigen presentation by murine epidermal cells.

The ability of epidermal Langerhans cells to present Ag for CD4-dependent immunity is well documented, and it has been hypothesized that Langerhans cells participate in the generation of immunity against incipient epidermal neoplasms by presentation of tumor-associated Ag in situ. This study examined the ability of murine epidermal cells (EC) to present tumor-associated Ag for the induction of in vivo antitumor immunity. Murine epidermal cells were deleted of Thy-1-bearing cells, cultured in 50 U/ml granulocyte-macrophage-CSF for 14 to 18 h, and pulsed with tumor fragments (TF) derived from S1509a-fibrosarcoma cells. These TF-pulsed EC were injected s.c. into syngeneic recipients at weekly intervals for a total of three immunizations and challenged with viable S1509a tumor cells 1 wk after the last immunization. Control animals received TF-pulsed allogeneic EC or EC treated identically but not pulsed with TF. EC that were pulsed with tumor cell fragments were able to induce protective immunity to tumor growth in vivo and to immunize for a significant delayed-type hypersensitivity response to injected tumor cells. The induction of antitumor immunity with TF-pulsed EC was genetically restricted, and culture of EC in granulocyte-macrophage-CSF was required for development of significant immunity. Furthermore, deletion of I-A+ cells by antibody and complement-mediated lysis eliminated the generation of immunity. Thus, I-A+ epidermal cells are capable of presenting S1509a tumor Ag for the generation of protective antitumor immunity in vivo.

Animals↗

PubMedDate not supplied

Aqueous humor inhibits epidermal cell antigen-presenting function.

Aqueous humor (AH) is a complex biological fluid containing factors that mediate a number of activities that may contribute to immune privilege in the anterior chamber of the eye. To determine whether AH may inhibit dendritic cell antigen-presenting function, we evaluated the ability of AH to alter the ability of freshly obtained epidermal cell (EC) preparations enriched for Langerhans cells (LC) to present tumor-associated antigens (TAA) derived from the S1509a spindle cell tumor for elicitation of a delayed-type hypersensitivity (DTH) reaction in tumor-immune mice. Fresh EC preparations contain 2-5% LC. Exposure of EC to media containing AH for 2 hours prior to TAA-pulsing and injection into a hind footpad of tumor-immune mice resulted in a dose-dependent decrease in the DTH response. Aqueous humor contains transforming growth factor-beta (TGF beta), primarily TGF beta 2 as determined by specific neutralization of activity in the Mv 1 Lu cell assay. However, exposure of EC to TGF beta 2 in this fashion prior to TAA-pulsing had no effect on the degree of hypersensitivity elicited. Furthermore, preincubation of AH with neutralizing antiserum to TGF beta 2 had no effect on the ability of AH to inhibit LC antigen-presenting function. Mixing of AH-exposed non-TAA-pulsed EC with TAA-pulsed EC not exposed to AH prior to footpad challenge did not diminish the DTH response, suggesting that carryover of AH into the footpad was not responsible for the inhibition observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMedDate not supplied

Modulation of antigen-presenting cell function as a potential regulatory mechanism in tumor-host immune reactions.

A growing body of information suggests that immunological defense mechanisms against newly emerging tumors may exist within the skin. In this regard, the recognition and presentation of tumor-associated antigens by cutaneous antigen presenting cells is a prerequisite for the establishment of specific tumor immunity. However, despite the recently demonstrated ability of normal I-A+ epidermal cells (Langerhans cells) to effectively present tumor-associated antigens in vivo, even tumors with recognizable antigenic epitopes can grow progressively in situ. Therefore, regulatory mechanisms within the local microenvironment may exist that control the ability of resident epidermal APC to initiate and to elicit protective immunity against incipient cutaneous neoplasms. This report reviews the role of APC in tumor immunity and the effects of cytokines and ultraviolet radiation (UVR) on tumor antigen presentation by epidermal APC. Our data suggest that these agents can significantly modify the ability of epidermal cells to present tumor-associated antigens and may therefore control the type and effectiveness of tumor immune responses in situ. Furthermore, the induction of primary tumor immunity and the elicitation of secondary immune responses are independently regulated and respond differently to cytokine application.

Antibody Formation↗