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M L Kapsenberg

Publications and source records attributed to M L Kapsenberg.

At least 91 records · Page 5Linked to original sources
PubMed1990

Comparison of diversity and function of house dust mite-specific T lymphocyte clones from atopic and non-atopic donors.

Panels of CD4+CD8- T lymphocyte clones (TLC), specific for house dust mite Dermatophagoides pteronyssinus (Dp) proteins, were generated from the peripheral blood of an atopic Dp-allergic donor (AD), suffering from severe atopic dermatitis, and a histocompatible non-atopic donor (NAD). We studied the diversity of TLC within these two panels in search for the possible occurrence of dominant clone types with properties that might be characteristic for the atopic or non-atopic state. TLC with specificities for at least four different Dp proteins were found within the panel from AD "L" and for at least three different Dp proteins within the panel from NAD "K". In addition, both panels showed a considerable but comparable restriction diversity within HLA-DR. Despite the diversity within the panels, all Dp-specific TLC from AD were found to produce IL 4, after HLA class II-restricted Dp-specific stimulation, whereas the TLC from NAD produced no or only minimal amounts of this lymphokine. Only supernatants from stimulated AD TLC could induce IgE secretion by B cells from NAD. Conclusively, these observations do not give evidence for the occurrence of an abnormal Dp-specific T cell repertoire in AD, but rather suggest aberrant secretion of the IgE-inducing lymphokine IL 4 by CD4+ Dp-specific T cells from AD.

Allergens↗
PubMed1990

T-cell receptor gamma delta bearing cells in normal human skin.

T-cell antigen receptors (TCR) are divided into common alpha beta and less common gamma delta types. In the murine skin, TCR gamma delta+ cells have been reported to form the great majority of epidermal T lymphocytes. We have examined the relative contribution of TCR alpha beta+ and TCR gamma delta+ cells to the T-cell population in normal human skin. Serial sections of freshly frozen skin specimens were acetone fixed, incubated with anti-CD3, beta F1 (anti-TCR alpha beta), anti-TCR gamma delta-1 and anti-TCR delta 1 (anti-TCR gamma delta) monoclonal antibodies (MoAb), and stained with a highly sensitive method. Over 90% of the T cells of normal human skin are localized around the postcapillary venules of the dermis, while less than 5% are present within the epidermis. In papillary dermis, TCR gamma delta+ cells formed on average 7% (anti-TCR gamma delta-1) or 9% (anti-TCR delta 1) of the total number of CD3+ cells, while TCR alpha beta+ cells constituted up to 80%. In epidermis, these percentages were 18% and 29% for TCR gamma delta+ cells, and up to 60% for TCR alpha beta+ cells. It is concluded that there is no preferential immigration or in situ expansion of TCR gamma delta+ T cells in normal human skin, because the relative percentages found for the TCR alpha beta+ and TCR gamma delta+ populations in skin are comparable to those found in lymphoid organs and peripheral blood. However, the percentage of TCR gamma delta+ cells in epidermis seemed on average higher than in papillary dermis. Therefore, there may still be a difference in migration patterns of TCR gamma delta+ v TCR alpha beta+ cells, but this does not result in their preferential localization in human epidermis. The hypothesis that TCR gamma delta+ T cells have a specialized function in immunosurveillance of epithelia may thus not be valid for human epidermis.

Antigens, CD↗
PubMed1990

Human epidermal Langerhans cells undergo profound morphologic and phenotypical changes during in vitro culture.

Morphology, phenotype, and enzyme activity of highly enriched (80%) unlabeled human epidermal Langerhans cells (LC) have been studied, with emphasis on changes during a short-term culture of three days in vitro. All freshly isolated LC contained Birbeck granules and expressed high levels of CD1a, CD1c, and MHC class II molecules HLA-DR, -DP, and -DQ. They have a weak to moderate expression of RFD1, C3biR, Fc gamma R, p 150/95, MHC class I molecules HLA-ABC, and of the adhesion molecules LFA-3 and ICAM-1, whereas no expression of LFA-1 and several monocyte/macrophage markers were detected. Human LC undergo profound changes during in vitro culture. Birbeck granules, C3biR, Fc gamma R, and p 150/95 were completely lost and the expression of CD1a and CD1c was markedly decreased or lost. Expression of molecules that have essential functions in antigen presentation remained present at the same level (MHC class II molecules and ICAM-1) or was markedly enhanced (LFA-3 and MHC class I). Highly remarkable was the dramatically enhanced expression of interdigitating cell marker RFD1. The monocyte/macrophage markers initially absent remained absent and the enzyme activity initially present (including ATPase and nonspecific esterase) remained present. In conclusion, the results in this report stress rapid alterations of human LC during in vitro culture, resulting in transformation into cells that have phenotypical characteristics of potent antigen presenting cells that resemble interdigitating cells.

Animals↗
PubMed1989

The restrictive role of sialic acid in antigen presentation to a subset of human peripheral CD4+ T lymphocytes that requires antigen-presenting dendritic cells.

Dendritic cells from human epidermis, i.e., Langerhans cells (LC), are more potent antigen-presenting cells (APC) than APC from peripheral blood in proliferative in vitro responses of helper T lymphocytes to various soluble antigens. Analysis of antigen recognition by CD4+ T lymphocyte clones indicated that this increased potency of LC as APC results from a preferential requirement for LC of part of the T cell population. These T cells show a long-lasting restoration of antigen responsiveness to peripheral blood APC after antigen-specific restimulation in vitro, indicating that restrictive antigen recognition concerns T cells that are not fully differentiated. A similar restrictive antigen recognition was observed by treatment of the T cells or the APC with neuraminidase. This restoration of responsiveness is associated with the occurrence of nonspecific cell clustering between T cells and APC. These results suggest that the selective requirement for APC is regulated by the function of adhesion molecules that are functionally blocked by sialic acid groups on immature peripheral T cells but that are readily available on peripheral T cells at a later stage of differentiation.

Antigen-Presenting Cells↗
PubMed1989

Predominance of "memory" T cells (CD4+, CDw29+) over "naive" T cells (CD4+, CD45R+) in both normal and diseased human skin.

Absolute numbers of CD3+ T lymphocytes and their subpopulations were determined and statistically evaluated in the lesional skin of psoriasis, atopic dermatitis, nummular dermatitis, pityriasis rosea, and lichen planus. Skin sections were divided into horizontal layers and the numbers of CD3+ T cells as well as CD4+ inducer and CD8+ suppressor-cytotoxic T-cell subsets were counted. In addition, absolute numbers of the two subpopulations of inducer T cells, i.e., "memory" (4B4+ 2H4-) and "naive" (4B4- 2H4+) were evaluated. Unexpectedly, epidermal infiltration by T cells was highest in psoriasis and lowest in atopic dermatitis. In most cases, this exocytosis was dominated by CD8+ suppressor/cytotoxic T lymphocytes, with a minimal epidermal mean CD4/mean CD8 ratio of 0.04 in pityriasis rosea and a maximum of 0.48 in psoriasis. Inducer T cells within the epidermis were almost exclusively of the 4B4+ 2H4- "memory" T-cell subpopulation, whereas 4B4- 2H4+ "naive" T cells were extremely uncommon in lesional epidermis. Similar results were obtained for dermal T cells in all diseases studied, i.e., 4B4- 2H4+ "naive" T cells were relatively rare. Papillary dermis infiltration by T cells was highest in lichen planus where a mean CD4/mean CD8 ratio of 1.10, the minimum in this comparative study, was obtained. The mean CD4/mean CD8 ratio of the papillary infiltrate was highest in atopic dermatitis (4.12). Our results indicate disease-specific and significantly different infiltration patterns of T-lymphocyte subsets in the chronic inflammatory dermatoses investigated.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed1989

Immunology of contact dermatitis.

Allergic contact dermatitis is a classical type IV delayed hypersensitivity immune response. This cell-mediated response is also known as hapten-type delayed hypersensitivity. Allergic contact dermatitis may be viewed as hyperreactivity of the skin immune system. In the present view of allergic contact dermatitis, individuals are born in a state of tolerance to environmental haptenic allergens. During life, sensitization to any hapten(s) may occur. Subsequent elicitation of a sensitized individual then leads to dermatitis, often accompanied by severe pruritus. Human epidermal Langerhans cells play a central role during the sensitization stage. These antigen presenting dendritic cells, loaded with environmental haptens, continuously leave the epidermis through the lymph vessels and, upon arrival in the paracortical T-cell areas of the skin draining lymph nodes, they differentiate into interdigitating cells. There is now in-vitro evidence for such a maturation of human Langerhans cells into interdigitating cells. Any given individual may be sensitized to any particular hapten by this route. Allergic contact dermatitis is probably a skin-specific disease because of the capacity of Langerhans/interdigitating cells to induce relatively naive T-cells to become memory T-cells. Factors determining the ultimate outcome in this continuous hapten presenting process, i.e. whether or not the original state of tolerance will persist, are still enigmatic. During elicitation, when the allergenic hapten is applied epicutaneously to a sensitized individual, a focal accumulation of immune response associated cells producing a wide variety of cytokines and inflammatory mediators ultimately results in the clinical condition of allergic contact dermatitis. Langerhans cells do not seem to play a major role during this stage.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Direct and indirect nickel-specific stimulation of T lymphocytes from patients with allergic contact dermatitis to nickel.

Fourteen T lymphocyte clones (TLC) specific for the contact allergen nickel were prepared either from lesional tissue biopsies or from peripheral blood of patients with allergic nickel-contact dermatitis. Two nickel-specific TLC, obtained from lesional tissue, responded to nickel without the participation of antigen-presenting cells (APC). This direct stimulation by nickel was not restricted by major histocompatibility complex-encoded molecules, since antibodies against HLA class I and II molecules did not block nickel-specific proliferation. Proliferation of other nickel-specific TLC was dependent on the presence of APC and was diversely restricted by HLA class II molecules. With one exception, the restriction determinants were present on HLA-DR and HLA-DQ molecules. Four TLC recognized nickel in association with subtypes of these serologically defined molecules. Five TLC seemed to recognize nickel in the context of highly unusual restriction determinants, since their restrictions could not be explained by the function of single polymorphic HLA class II epitopes. The absence of HLA class II restrictions and the occurrence of deviant HLA class II restrictions in part of the nickel-specific TLC are suggested to result from direct interactions of nickel with critical immune response molecules.

Antigen-Presenting Cells↗
PubMed1988

Enrichment of unlabeled human Langerhans cells from epidermal cell suspensions by discontinuous density gradient centrifugation.

In this report we introduce an alternative procedure for enrichment of human epidermal Langerhans cells (LC) from epidermal cell suspensions of normal skin. By means of discontinuous Ficoll-Metrizoate density gradient centrifugation, a fraction containing high numbers of viable, more than 80% pure LC was recovered, as judged by CD1a expression. The purity of the LC-enriched fraction appeared to be dependent on the percentage LC in the crude epidermal cell suspension. LC enriched by this method retained their accessory and antigen-presenting capacities, as determined in the Concanavalin-A induced T-cell response, in the allogeneic mixed leukocyte reaction and in the antigen-specific T-cell proliferation assay in vitro. The great advantage of this method is that it is simple and rapid and that the isolated LC are unlabeled.

Antigen-Presenting Cells↗
PubMed1987

Nickel-specific T lymphocyte clones derived from allergic nickel-contact dermatitis lesions in man: heterogeneity based on requirement of dendritic antigen-presenting cell subsets.

Inflammatory skin T cells were cloned in an antigen-independent way from lesions of patients with experimentally induced nickel-contact dermatitis. In three experiments 7-15% of the CD4+8- T lymphocyte clones (TLC) appeared to be specific for nickel in a proliferation assay. These proliferative response of nickel-specific TLC required the presence of antigen-presenting cells (APC) and were restricted by HLA class II molecules. All TLC recognized nickel presented by APC from epidermal skin. Remarkably, 5 out of 8 nickel-specific TLC exclusively recognized nickel when presented by these skin-specific APC whereas 3 out of these 8 clones could also recognize nickel presented by APC from peripheral blood. The critical APC within the fractions of epidermal cells and peripheral blood appeared to belong to the family of dendritic cells, i.e. Langerhans cells and circulating dendritic cells, respectively.

Antigen-Presenting Cells↗
PubMed1987

Accessory cell requirements in mitogen-induced rabbit T lymphocyte proliferation in an improved tissue culture system.

The impact of an improved culture medium (IMDM+), consisting of Iscove's modified Dulbecco's medium supplemented with albumin, transferrin, insulin, zinc, 2-mercapthoethanel, and 0.1% fetal bovine serum was investigated in phytohemagglutinin (PHA)-induced rabbit T cell proliferation. At the number of 2 X 10(5) cells/well purified T lymphocytes cultured in IMDM+ responded 3 to 10 times better than lymphocytes cultured in serum-supplemented RPMI 1640 medium. In these conditions, PHA-induced proliferation seemed not to require the presence of accessory cells. However, at lower cell numbers, T cell proliferation was more efficient when calculated on a per cell basis. At these low cell numbers, optimal proliferation required accessory cells like macrophages or dendritic cells. The apparent absence of this requirement for accessory cells at high T cell concentrations may be explained by the contribution of contaminating macrophages and dendritic cells in the purified T cell fractions.

Animals↗
PubMed1987

The crucial role of human dendritic antigen-presenting cell subsets in nickel-specific T-cell proliferation.

In the majority of patients, allergic nickel contact dermatitis is associated with a proliferative response of peripheral blood T lymphocytes to nickel sulfate. Optimal proliferation was found in a concentration range of 1-2 X 10(-4) M nickel sulfate. Nickel-specific response of purified peripheral blood T cells requires the presence of antigen-presenting cells (APC). Both peripheral blood monocytes and skin-derived epidermal cells could function as APC, but epidermal cells were shown to be more potent than monocytes. By testing FcR+ monocytes and FcR- circulating dendritic cells for their antigen-presenting capacities, it was found that the critical APC within the fraction of monocytes is the circulating dendritic cell. Testing highly purified T6+ (CD 1) skin-specific dendritic cells (Langerhans cells, LC) and T6- epidermal cells as APC, the critical APC within the fraction of epidermal cells appeared to be the LC. The crucial role of LC was stressed in experiments using T cells from patients exhibiting a positive patch test to nickel but a low or absent proliferative response to nickel by unpurified peripheral blood cells. Whereas addition of peripheral blood APC was ineffective, addition of LC to purified peripheral T cells was shown to overcome this low responsiveness to nickel. These results indicate the crucial role of dendritic APC subsets in nickel-specific T-cell proliferation.

Antigen-Presenting Cells↗
PubMed1987

The skin immune system (SIS): distribution and immunophenotype of lymphocyte subpopulations in normal human skin.

The complexity of immune response-associated cells present in normal human skin was recently redefined as the skin immune system (SIS). In the present study, the exact immunophenotypes of lymphocyte subpopulations with their localizations in normal human skin were determined quantitatively. B cells were not found to be present in normal human skin. Lymphocytes were always of T-cell type, and 90% of these T cells were clustered in 1-3 rows around postcapillary venules of the papillary vascular plexus or adjacent to cutaneous appendages. In such perivascular localizations, they were found to differ from their circulating counterparts in three ways. First, skin perivascular cells were found to be approximately evenly distributed over CD4+ inducer and CD8+ suppressor-cytotoxic T-cell subsets (mean CD4/CD8 ratio: papillary layer 0.96, reticular layer 0.99). Second, within the category of CD4+ inducer T cells, most were phenotyped as CD4+, 4B4+ helper inducer T lymphocytes, whereas CD4+, 2H4+ suppressor inducer T lymphocytes were found to be relatively rare (less than 5%). Third, the majority of skin perivascular T cells were activated as they expressed HLA-DR and interleukin 2 receptors. Intraepidermal, directly subepidermal, and other ("free") lymphocytes were mostly of the CD8+ suppressor-cytotoxic T-cell subset but accounted for less than 10% of the total number of lymphocytes. Intraepidermally localized T cells accounted for less than 2% of the total number of lymphocytes present in normal skin. Our results indicate that preferential perivascular localization of activated T lymphocytes is the characteristic of normal human skin. This might be a reflection of continuous antigen recognition upon endothelial cell presentation and/or continuous T cell-mediated endothelial cell activation thereby inducing enhanced antigen clearing by the skin's endothelium.

B-Lymphocytes↗
PubMed1986

Antigen-presenting cell function of dendritic cells and macrophages in proliferative T cell responses to soluble and particulate antigens.

The capacity of dendritic cells (DC) and macrophages (M phi) to present soluble and particulate antigen was tested in an ovalbumin (OVA)-specific T cell proliferation assay. In a comparative investigation we found that both DC and M phi were able to present soluble OVA, but that only M phi could present insolubilized OVA to T cells. DC were found to be able to present OVA in collaboration with M phi. The failure of DC to present insolubilized OVA is probably caused by their inability to endocytose these antigens. DC appeared not to endocytose substantial amounts of soluble OVA either. In contrast to M phi, antigen presentation by DC is not blocked by lysosomotropic drugs. Taken together, these observations suggest that DC can present soluble protein antigens without intracellular degradation.

Animals↗
PubMed1985

Dendritic cells as accessory cells in antigen-specific murine T lymphocyte proliferation in vitro.

The role of dendritic cells in antigen-induced murine T lymphocyte activation was studied by addition of purified dendritic cells to purified lymph node T lymphocytes from ovalbumin-primed mice. In the presence of the priming antigen T cells generated an antigen-specific response. The response was at least 3-fold higher with the use of a modified IMDM culture medium. The complete requirement for accessory cells was demonstrated only when nylon wool-purified T lymphocytes were thoroughly depleted of Ia antigen-expressing cells. Dendritic cells as well as peritoneal exudate macrophages were equally effective as antigen-presenting cells.

Animals↗
PubMed1985

Characterization of dendritic cells, isolated from normal and stimulated lymph nodes of the rat.

Non-lymphoid dendritic cells were isolated from normal and paratyphoid vaccine-stimulated lymph nodes draining the rat skin. They were studied using enzymecytochemical, immunocytochemical and electron-microscopical methods. These cells had an irregular outline and an eccentrically situated nucleus. All showed acid phosphatase activity in a central area and expressed Ia antigen on the plasma membrane. Birbeck granules were exclusively present in dendritic cells isolated from lymph nodes in the induction phase of the immune response. This observation concurs with the presence of Birbeck granules in interdigitating cells in situ during the same period of the immune response. It is concluded that the dendritic cells are the in-vitro equivalents of the non-actively phagocytizing population of interdigitating cells.

Acid Phosphatase↗
PubMed1985

Differential requirements for rabbit dendritic cells and macrophages in T lymphocyte proliferation induced by various mitogens.

Dendritic cells have been isolated from rabbit lymph nodes. Morphologically and phenotypically, they resemble dendritic cells from the mouse and rat. A comparison was made of the accessory cell function of dendritic cells and peritoneal macrophages in T-cell proliferation induced by phytohaemagglutinin (PHA) or Con A, or by a simultaneous treatment with the enzymes neuraminidase and galactose oxidase (NaGo). Dendritic cells seemed to be more effective than macrophages as accessory cells in these assays. However, macrophages suppress lymphocyte proliferation through the release of oxidating agents and production of prostaglandins. Elimination of this suppressive effect of the macrophages by addition of a combination of 2-mercaptoethanol (2-ME) and indomethacin in PHA-induced cell proliferation resulted in a much higher support by macrophages, giving results that were comparable to those obtained with dendritic cells, but in NaGo-induced proliferation, macrophages were still not as effective as dendritic cells in the presence of the drugs. Experiments in diffusion culture vessels and with interleukin-1-containing macrophage supernatants showed that support by accessory cells can be mediated by soluble factors in PHA-induced proliferation. In contrast, in NaGo-induced proliferation, lymphocytes and accessory cells have to interact directly.

Animals↗