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Biomedical subjects

A Cavani

Publications and source records attributed to A Cavani.

29 records · Page 2Linked to original sources
PubMed1997

Antibodies against sialophorin (CD43) enhance the capacity of dendritic cells to cluster and activate T lymphocytes.

CD43 is a leukocyte membrane glycoprotein rich in negatively charged sialic acid residues that may act as an anti-adhesion molecule. In this study, we analyzed the expression and function of CD43 on epidermal Langerhans cells (LC) and dendritic cells derived from adherent peripheral blood monocytes treated with granulocyte-macrophage CSF and IL-4 (Mo-DC). Both freshly isolated LC (fLC) and Mo-DC expressed uniformly high amounts of membrane CD43, with levels unchanged in 48-h cultured LC or in TNF-alpha-treated Mo-DC. When fLC or Mo-DC were transiently preincubated with anti-CD43 mAb or neuraminidase, they formed much larger clusters with T cells as compared with cells incubated with control mAb. Moreover, a significantly increased proliferation of naive allogeneic T cells in a primary MLR assay was induced. Anti-CD43-treated Mo-DC also presented tetanus toxoid to primed T cells more efficiently. Immunofluorescence and immunogold electron microscopy showed that following Ab cross-linking and warming to 37 degrees C, CD43 is progressively removed from the cell surface and is internalized within endosomes and vacuoles. In addition, fLC and Mo-DC incubated with anti-CD43 mAb increased expression of HLA-DR, ICAM-1, B7-1, B7-2, CD40, and CD83 after 24 h, and this was partially prevented by culturing cells in the presence of cycloheximide. We thus postulate that membrane CD43, other than serving as anti-adhesion molecule, can mediate activation signals in immature DC, leading to augmented expression of adhesion/costimulatory molecules and Ag-presenting function.

Antibodies, Monoclonal↗
PubMed1996

Epidermal cytokine and neuronal peptide modulation of contact hypersensitivity reactions.

Cellular and molecular mechanisms underlying contact hypersensitivity reactions have been, and still are, fields under intense investigation, not only for the importance of these reactions in clinical medicine, but also because they are considered prototypic of a vast group of T cell-mediated immune diseases of the skin. Interestingly, potent contributions by non-bone marrow-derived cells have been shown clearly, demonstrating that epidermal cells are far more than mere spectators of these reactions, and undergo a functional activation after contact with the hapten causing the hypersensitivity reaction. In particular, keratinocyte contribution to the onset as well as modulation of contact hypersensitivity reactions through the release of a plethora of cytokines, has been widely documented. Moreover, an important control over these reactions is exerted by local release of neuropeptides by nerve endings. This review paper focuses on epidermal cytokine and neuronal peptide modulation of contact hypersensitivity reactions, trying to document the complexity of the regulatory systems, active during these immune processes of the skin.

Animals↗
PubMed1995

Characterization of epitopes recognized by hapten-specific CD4+ T cells.

Although protein-derived nominal Ags have, in many instances, been precisely determined, the epitopes recognized by hapten-specific CD4+ T cells responsible for contact sensitization have not been defined. To better understand the nature of the precise epitopes generated after hapten interaction with Langerhans cells (LC), we assessed the ability of TNP-modified I-Ak- and I-Au-binding peptides to activate hapten-specific CD4+ T cells obtained respectively from TNCB-primed C3H (H-2k) and PL/j (H-2u) mice. Using LC as APC, I-Ak-restricted TNP-specific CD4+ T cells proliferated in the presence of the synthetic peptide hen egg lysozyme 52-61 derivatized with TNP at position 56, and less so when TNP was coupled at positions 53 or 59. Similarly, I-Au-restricted TNP-specific CD4+ T cells from PL/j mice were triggered by the synthetic I-Au-binding 13 mer poly(A)-Y5-R6 TNP-modified at position 4, and to a limited extent with TNP coupled in positions 7 or 10. Our results indicate that hapten-modified MHC class II binding nonautologous peptides are recognized by hapten-specific CD4+ T cells and that precise positioning of hapten molecules on peptides binding MHC class II molecules is required for optimal CD4+ T cell recognition. These findings provide insight into the manner in which haptens are recognized by T cells involved in contact sensitivity and should facilitate the study and design of specific therapies for the manipulation of hapten-specific CD4+ T cell responses.

Amino Acid Sequence↗
PubMed1995

Establishment of a cell line with features of early dendritic cell precursors from fetal mouse skin.

During ontogeny, the skin is progressively populated by major histocompatibility complex class II-negative dendritic cell (DC) precursors that then mature into efficient antigen-presenting cells (APC). To characterize these DC progenitors better, we generated myeloid cell lines from fetal mouse skin by infecting cell suspensions with a retroviral vector carrying an envAKR-mycMH2 fusion gene. These cells, represented by the line FSDC, displayed a dendritic morphology and their proliferation in serum-free medium was promoted by granulocyte/macrophage colony-stimulating factor (GM-CSF), but not macrophage-CSF. FSDC expressed strong surface-membrane ATP/ADPase activity, intracellular staining for 2A1 antigen, and a surface phenotype consistent with a myeloid precursor: H-2d,b+, I-Ad,b+, CD54+, CD11b+, CD11c+, 2.4G2+, F4/80+, CD44+, 2F8+, ER-MP 12-, Sca-1+, Sca-2+, NLDC-145-, B7.2+, B7.1-, J11d-, B220-, Thy-1-, and CD3-. FSDC stimulated poorly allogeneic or syngeneic T cells in the primary mixed-leukocyte reaction, and markedly increased this function after treatment with GM-CSF, GM-CSF and interleukin (IL)-4 or interferon-gamma (IFN-gamma); in contrast, stem cell factor, IL-1 alpha and tumor necrosis factor-alpha had no effect. Preculture with IFN-gamma was required for presentation of haptens to primed T cells in vitro. However, FSDC, even after cytokine activation, were less potent APC than adult epidermal Langerhans cells in both of the above assays. Finally, FSDC derivatized with haptens and injected either intravenously or subcutaneously could efficiently induce contact sensitivity responses in naive syngeneic mice. The results indicate that fetal mouse skin is colonized by myeloid precursors possessing a macrophage/immature DC-like surface phenotype and priming capacity in vivo. These cells need further differentiation and activation signals (e.g. cytokines) to express their antigen presenting potential in vitro.

Animals↗
PubMed1994

Integrin expression in middle ear cholesteatoma.

Cholesteatoma is lined by a squamous keratinizing epithelium exhibiting most of the features of normal epidermis. In this study, we investigated by immunohistochemistry the expression of integrin adhesion molecules in primary acquired and recurrent cholesteatomas, and compared it with common epidermal cysts and normal human skin. The results showed that cholesteatoma epithelium exhibited a markedly augmented expression of alpha v integrin subunit and a corresponding increased deposition of vitronectin (alpha v ligand) in the surrounding stroma as compared to epidermal cyst and normal human skin. In contrast, the expression pattern of alpha 2 beta 1, alpha 3 beta 1, and alpha 6 beta 4 integrins as well as the distribution of laminin, collagen IV and fibronectin were similar in cholesteatomas, epidermal cysts and normal human skin. Similar staining pattern was observed in primary acquired and recurrent cholesteatoma.

Antigens, CD↗
PubMed1993

Phosphatidylserine enhances the ability of epidermal Langerhans cells to induce contact hypersensitivity.

Phosphatidylserine (PS) modulates several immune functions in vitro, including T cell activation, antibody and cytokine production, and macrophage growth. In the present work we studied the effects of PS on the induction of contact hypersensitivity (CH) in mice. BALB/c mice painted with PS (9.4-75 mg/kg) and with a sensitizing dose of DNFB or oxazolone on the same skin site exhibited a dose-dependent augmentation of CH reactions to either DNFB (> 60%) or oxazolone (> 35%), respectively. Bovine brain PS-enriched phospholipid mixture, lyso-PS, and dipalmitoyl-PS also induced similar enhanced CH responses, whereas phosphatidylglycerols had no effect. Increased CH was observed only when PS was applied from 2 days before to 12 h after DNFB. Immunization of naive syngeneic mice with skin grafts that were treated with PS and DNFB also led to enhanced (> 50%) CH responses. In addition, immunization by iv injection of epidermal cell suspensions enriched for Langerhans cells (LC) or of purified LC that were treated with PS (1-100 microM, 30 min, 37 degrees C), and then modified in vitro with DNBS (1 mg/ml, 30 min, 37 degrees C) led to increased (> 30-75%) CH responses in recipient syngeneic animals. Finally, adoptive transfer of DNFB-immune lymph node cells obtained from mice that were treated with PS induced augmented CH responses in recipient animals. The results suggest that PS is capable of up-regulating the induction of CH in mice by stimulating the APC function of epidermal LC.

Animals↗
PubMed1993

Distinctive integrin expression in the newly forming epidermis during wound healing in humans.

The integrin receptor family plays a fundamental role in mediating cell attachment to a variety of extracellular matrix molecules. In normal human epidermis, the alpha 2 beta 1, alpha 3 beta 1, alpha 6 beta 4, and alpha v beta 5 integrin heterodimers are expressed and appear largely confined to the basal cell layer. In the present study, beta 1, beta 4, and alpha v integrin expression in the epidermis during wound healing in humans was examined. Punch biopsies were performed on healthy volunteers. At daily intervals up to day 8, and at days 11, 14, 21, and 28, the wound site was surgically removed. Using immunofluorescence microscopy, several modifications of the integrin expression pattern were observed on migrating keratinocytes during the re-epithelialization phase of the wound-healing process: i) alpha v expression was strongly enhanced and polarized at the basal pole of basal keratinocytes; ii) among the beta 1 integrins, alpha 3 beta 1 was overexpressed and distributed over the entire basal keratinocyte membrane and a weak alpha 5 beta 1 reactivity became evident; and iii) alpha 6 beta 4 was detected as a linear staining along the newly forming dermal-epidermal junction. Moreover, both during the re-epithelialization phase and during the first 2 weeks after wound closure, alpha 3, alpha 6, alpha v, beta 1, and beta 4 were no longer confined to the basal layer, as in normal epidermis, but were also found on several suprabasal cell layers. These results suggest that alpha v beta 5, alpha 3 beta 1, and alpha 5 beta 1 may be the main integrin receptors mediating keratinocyte spreading and migration over the provisional matrix of the wound bed.

Adult↗
PubMedDate not supplied

New insights into the pathomechanisms of contact dermatitis by the use of transgenic mouse models.

Allergic contact dermatitis (ACD) is one of the most common skin diseases with a great socioeconomic impact. Although extensively studied, its pathophysiology and the interaction of different cells and factors which lead to sensitization and elicitation reaction are still not completely understood. The advent of transgenic mouse technology has considerably changed the study of ACD. This technology has been used extensively to investigate biomedically important issues in such diverse areas as mammalian development, neurophysiology and immunology. This new approach has already led to fascinating results which are confirmatory but also contradictory to previous thinking on the role of certain cytokines, adhesion and cell surface molecules in the complex pathophysiologic process of ACD. This review will describe how recent experiments employing mice carrying cytokine and accessory molecule transgenes change our current understanding of contact dermatitis which may lead to improved therapeutic strategies.

Animals↗