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J D Bos

Publications and source records attributed to J D Bos.

At least 145 records · Page 8Linked to original sources
PubMed1992

Th1 lymphokine production profiles of nickel-specific CD4+T-lymphocyte clones from nickel contact allergic and non-allergic individuals.

Panels of nickel-specific T-lymphocyte clones (TLC) were prepared from nickel-allergic and non-allergic donors. TLC from both panels showed similar levels of expression of TCR alpha/beta, CD4, CD2, CD25, and CD29 and recognized nickel in association with class II HLA molecules with restriction determinants in HLA-DR, HLA-DP, and HLA-DQ. The lymphokine secretion was analyzed in TLC from both panels upon antigen-specific or non-specific stimulation and was compared with the secretion profiles of representants of pre-established human atopen-specific Th1 and Th2 cells. Nickel-specific TLC from both panels showed a lymphokine secretion pattern similar to the atopen-specific Th1 cells, although there was some variation from clone to clone. Most TLC secreted substantial amounts of IFN-gamma, IL-2, TNF-alpha, and GM-CSF, but little or no IL-4 and IL-5. The variation observed mainly concerned IL-2 secretion that could be low or absent in some of the TLC. The general secretion pattern did not change upon different modes of stimulation, including activation via CD3, CD2, or CD28. Because nickel-specific TLC from allergic and non-allergic individuals show a similar Th1 secretion pattern, the present results give no evidence that aberrant lymphokine secretion by CD4+T cells determines the contact allergic state, as was found for atopic allergy in a previous study.

CD4-Positive T-Lymphocytes↗
PubMed1992

Molecular heterogeneity of the fourth component of complement (C4) and its genes in vitiligo.

In view of evidence suggesting vitiligo is an autoimmune disease, we investigated whether vitiligo is associated with inherited deficiencies of the fourth (C4) and second (C2) component of complement and with certain human leukocyte antigens (HLA). Analysis of functional activities of C4 and C2 in sera of patients with vitiligo (n = 42) showed that 17% of them had a heterozygous C4 deficiency and 5% had a heterozygous C2 deficiency. In the normal control group (n = 30), 3% had a heterozygous C4 deficiency and none had a C2 deficiency. C4 typing by Western blot analysis showed the frequency of the C4A*Q0 allele in the vitiligo patient group to be close to normal. However, the frequency of one C4B*Q0 allele was three times higher, and that of two C4B*Q0 alleles five times higher in the vitiligo patient group than the reported frequencies in normal control groups. Southern blot analysis of Taq1 digests of DNA using C4 and 21-hydroxylase probes showed that two patients with two C4B*Q0 alleles had a deletion of a 21-OHA-C4B segment. In the other patients, having one or two C4B*Q0 alleles, these null alleles probably occurred due to a loss of C4 gene expression. HLA analysis did not show any allelic association of C4A*Q0 or C4B*Q0 with any HLA antigen in vitiligo, but confirmed the previous findings of a negative association with HLA-DR3 and a positive association with HLA-DR4. These results suggest that abnormalities of the C4B gene and the above-mentioned associations with HLA antigens may be some of the risk factors in vitiligo.

Adrenal Hyperplasia, Congenital↗
PubMed1992

The skin in severe combined immunodeficiency: a case with transient cutaneous presence of gamma/delta (TRC1+) T cells.

We report the case of a boy with severe combined immunodeficiency (SCID) and serious skin problems. The level of purine 5'-nucleotidase was greatly reduced in the lymphocytes of this patient. To our knowledge, no patients with SCID and this enzyme deficiency have been described previously. The relationship between reduced levels of this enzyme and the immunodeficiency is unclear. This case is also unusual because of the presence of large numbers of T lymphocytes expressing TCR1 (gamma/delta) in the skin. Moreover, the presence of so many TCR1-positive cells was not consistent with the low numbers of these cells in the peripheral blood. These cells were not present in skin biopsies taken at a later stage during the course of the disease. An oligoclonal lymphocytosis developed during follow-up, and a monoclonal antibody reactive with these clones was found, indicating that these lymphocytes were present in the skin. This case report illustrates the benefit of the use of monoclonal antibodies in identifying the cells involved in the cutaneous inflammation in SCID, in order to gain a better insight into the characteristics of these cells.

Antibodies, Monoclonal↗
PubMed1992

Mycobacterial 65,000 MW heat-shock protein shares a carboxy-terminal epitope with human epidermal cytokeratin 1/2.

Molecular mimicry between mycobacterial heat-shock protein (hsp) 65 and host tissue antigens have been implicated in the autoimmune pathogenesis of certain idiopathic diseases. Here, we demonstrated that two of our previously characterized monoclonal antibodies (mAb), Ne5 and Nd4 that were directed to a carboxy-terminal epitope on the mycobacterial hsp 65, specifically cross-reacted with suprabasal cytokeratin of the normal human skin. These mAb also showed similar keratin staining of hair follicle epithelia and produced no reaction with other dermal components. Both mAb strongly stained the cytoplasm of the majority of freshly isolated epidermal keratinocytes from the normal human skin. None of these mAb showed staining with human HeLa cells and with human skin fibroblasts. Immunoblotting using total keratin extract prepared from isolated epidermal keratinocytes revealed that mAb Ne5 and Nd4 specifically reacted with a molecular size of 65,000-67,000 MW keratin protein(s) and such reactivity was not observed from cytoskeletal proteins extracted from HeLa cells and skin fibroblasts. Comparison of immunoblotting reactivity with conventional anti-cytokeratin mAb further revealed that mAb Ne5/Nd4 recognized a 65,000-67,000 MW molecular-sized protein corresponding to cytokeratin 1/2 from the same keratinocyte extract as anti-cytokeratin mAb. Preincubation of mAb Ne5/Nd4 with the purified mycobacterial hsp 65 abolished this keratin cross-reactivity in both immunohistochemistry and immunoblotting. Moreover, these mAb showed no keratin staining in lesional psoriatic skin and also reacted weakly with cultured epidermal keratinocytes. Since mAb Ne5/Nd4 specifically recognized a 67,000-65,000 MW molecular-sized protein(s) derived from epidermal keratinocytes and the known characteristics of epidermal cytokeratin 1/2 appeared to be consistent with present results, we concluded that Ne5/Nd4 cross-reactive protein(s) in the human epidermis is suprabasal cytokeratin 1/2. Comparison of the previously mapped Ne5/Nd4 epitope region of amino acid residues 525-540 of the mycobacterial hsp 65 with the entire sequence of human 65,000 MW keratin revealed that a stretch of nine amino acids of the Ne5/Nd4 epitope sequence resembled certain regions of the carboxy-terminus of the human 65,000 MW keratin. This similarity of the mycobacterial hsp 65 probably contributes to the cytokeratin cross-reactive epitope. Our results presented here demonstrate direct evidence of immunological cross-reactivity between mycobacterial hsp 65 and human epidermal cytokeratin 1/2. We speculate that Ne5/Nd4 cross-reactive epitope of epidermal cytokeratins might be an important target for skin diseases.

Amino Acid Sequence↗
PubMed1992

Immune dysregulation in atopic eczema.

BACKGROUND: In this review, present knowledge of atopic eczema immunopathogenesis is summarized, emphasizing recent new findings. Systemic abnormalities in cell-mediated immunity have not been demonstrated firmly in patients with atopic eczema. Within the skin itself, there is evidence for decreased cell-mediated immunity, which is partially correlated with the severity of skin disease. Atopic eczema, however, cannot be regarded as a direct result of decreased cutaneous cell-mediated immunity, since immunophenotyping studies have revealed activated T cells as well as dendritic cells within involved skin. In addition, disease marker studies in peripheral blood indicate vigorous T-cell activation in atopic dermatitis. OBSERVATIONS: The original observation of IgE molecules on the membranes of Langerhans cells may indicate trapping of IgE allergen complexes, their processing, and subsequent presentation to allergen-specific T cells within involved skin. Recent findings as to the abnormal regulation of IgE synthesis in atopy point to a preferential expansion of interleukin 4 and interleukin 5 producing allergen-specific T cells, leading to increased production of interleukin 4 and thus increased levels of allergen-specific IgE. We have prepared atopic skin as well as peripheral blood-derived T-cell clones and determined their specificity and cytokine production profile. Results indicate in situ production of interleukin 4 and interleukin 5 within involved skin in response to environmental antigens. CONCLUSIONS: These new findings as to the basis of IgE dysregulation in atopy, as well as to the identification of an abnormal cytokine secretion pattern by T cells presumed to be central in immunopathogenesis of atopy-related disorders, suggest a distorted and cytokine-mediated self-perpetuating response of the skin immune system to environmental allergen(s) in the pathogenesis of skin disease in atopy. These observations may have important implications for the development of new therapies for atopic eczema.

Dermatitis, Atopic↗
PubMed1991

Human atopen-specific types 1 and 2 T helper cell clones.

Eight representative T lymphocyte clones (TLC) randomly selected from previously described panels of CD4+ housedust mite Dermatophagoides pteronyssinus (Dp)-specific TLC from atopic and nonatopic donors were studied in more detail in a comparative investigation. The TLC from the atopic donors closely resembled murine type 2 Th (Th2) cells by secreting substantial IL-4, IL-5, IL-6, TNF-alpha, and granulocyte-macrophage (GM)-CSF, minimal IFN-gamma, and relatively little IL-2. In contrast, the nonatopic's TLC resembled murine type 1 Th (TH1) cells by secreting substantial IFN-gamma, IL-2, TNF-alpha, and GM-CSF, no IL-4, and little IL-5. A difference with murine Th1 cells was their additional secretion of IL-6. These cytokine profiles were consistent upon stimulation via different activation pathways including stimulation with specific Dp Ag, mitogenic lectins, and antibodies to CD2, CD3, or CD28. The observed differences in IL-2 secretion, however, were most evident upon stimulation with anti-CD28. If TLC cells were cultured with highly purified B cells and stimulated with anti-CD3 in the absence of exogenous IL-4, IgE synthesis was induced only in cultures with the atopics' Th2 clones, which could be completely abrogated by anti-IL-4. The mere presence of exogenous rIL-4, however, did not result in IgE synthesis, nor did unstimulated TLC cells alone. But if unstimulated TLC cells (that proved not to secrete detectable amounts of cytokines) were added together with rIL-4, again IgE synthesis was induced only in cultures with the atopics' Th2 clones, suggesting the involvement of an additional, as yet unidentified accessory helper function of the atopics' Th2 clones for IgE induction. Unstimulated Th2 clones showed a significantly higher expression of CD28 than the Th1 clones, but three days after stimulation, CD28 expression was elevated to comparable levels on both subsets. When added to B cells at this time point, together with rIL-4 and anti-IFN-gamma, still only the atopics' Th2 clones supported IgE synthesis, arguing against a role for CD28 in this accessory helper function. Whereas the atopics' Th2 clones were excellent helper cells for IgE induction, a unique property of the nonatopic's Th1 clones was their cytolytic activity toward autologous APC which could be induced by specific Dp Ag and by anti-CD3. The present data provide clear evidence for the existence of Th1 and Th2 cells in man.

Allergens↗
PubMed1991

Functional subsets of allergen-reactive human CD4+ T cells.

After a period of resistance, the concept of human helper T (TH)-cell subsets is gaining currency. This is the result of analyses from a number of laboratories on the cytokine profiles of T-cell clones prepared from chronically-infected and hypersensitive individuals. Here, Martien Kapsenberg and colleagues summarize these studies and speculate on the significance of skewed TH1 and TH2 responses.

Allergens↗
PubMed1991

High frequency of IL-4-producing CD4+ allergen-specific T lymphocytes in atopic dermatitis lesional skin.

In atopic dermatitis (AD) hypersensitivity reactions to allergens are commonly observed and are assumed to make a major contribution in the pathomechanism of the disease. It may be expected that allergen-reactive Th cells play a central role in these reactions. In the present study the occurrence and function of allergen-specific T lymphocytes in dermal inflammatory lesions were studied. To this aim panels of randomly cloned CD4+ T cells from lesional skin biopsies of two housedust mite Dermatophagoides pteronyssinus (Dp)-allergic AD patients were screened for reactivity with Dp allergens. The results were compared with similar tests for Dp reactivity of T-lymphocyte clones (TLC) from the peripheral blood of these patients. In the panels of TLC generated from lesional skin (S-TLC), a considerable number of TLC appeared to be Dp-specific, 47% (n = 17) and 10% (n = 29), respectively. In the panels from the peripheral blood, the percentages of Dp-specific TLC were only 0% (n = 22) and 3% (n = 34), suggesting accumulation or expansion of these T cells in lesional skin. The function of these TLC was studied by assaying the secretion of IL-4 and IFN-gamma, which have been shown to be produced in aberrant ratios by Dp-specific TLC from the peripheral blood of AD patients (Wierenga et al: J Immunol 144:4651, 1990). All Dp-specific S-TLC produced IL-4 in combination with no or low levels of IFN-gamma, whereas many of the non-Dp-specific S-TLC and blood-derived TLC (B-TLC) were observed to produce high levels of IFN-gamma without significant amounts of IL-4. A functional consequence of these cytokine profiles was demonstrated by the finding that TLC producing substantial amounts of IL-4 enhanced expression of the low-affinity Fc receptor for IgE (CD23) on antigen-presenting cells to a greater extent than did IFN-gamma-producing TLC.

Adult↗
PubMed1991

Inhibitory effect of cyclosporin A on antigen and alloantigen presenting capacity of human epidermal Langerhans cells.

The effect of cyclosporin A (CyA) on the capacity of human epidermal Langerhans cells (LC) to stimulate allogeneic T cells or to present antigen to autologous T cells was investigated. Preparations of LC enriched by discontinuous density gradient centrifugation were pulsed for 2 or 16 h with graded doses (5-5000 ng/ml) of CyA prior to co-culture with T cells. Pretreatment of LC with CyA resulted in a dose-dependent decrease of the functional capacity of LC to stimulate T cells. This inhibition (up to 90%), already achieved after a pulse of 2 h, was not due to a cytotoxic effect of the drug and appeared to be reversible. The possibility that CyA exerted its effect indirectly on T cells via release of CyA from LC into the supernatant during co-culture was excluded. The suppression of immunostimulatory function was a direct effect of the drug on LC. CyA did not affect the production by LC of IL-1 or prostaglandin, nor the expression of MHC class II products HLA-D and RFD1 or adhesion molecules ICAM-1 and LFA-3. These results suggest that inhibition of contact allergic skin reactions by CyA may be due in part to an impairment of the function of LC.

Antigen-Presenting Cells↗
PubMed1991

Evidence for alpha-MSH binding sites on human scalp hair follicles: preliminary results.

Alpha-MSH, considered an important pigmentation hormone, binds to melanocytes and is thought to stimulate melanogenesis through a cyclic-AMP-dependent mechanism. The binding of alpha-MSH to follicular melanocytes has been investigated in human hair of different colors, ranging from black to blond and senile white. Hairs were plucked, the follicles were cut off, and an alpha-MSH binding assay, using a radiolabeled alpha-MSH analogue, was performed on these bulbs. As controls of each assay, fragments of hairs of the same person were used. The results show a dose-response relationship and the assay seems to be specific for alpha-MSH, because other peptides such as ACTH, beta-LPH and beta-endorphins do not compete for binding sites as alpha-MSH does. These binding sites seem to be present only on melanin synthesizing melanocytes, since the controls and follicles of senile white hair, which do not contain active melanocytes, show negative results. All the assays were performed on raw material, i.e., whole plucked hair follicles. This is the first time that binding sites for alpha-MSH have been demonstrated on human scalp hair follicles. In addition, their presence was found to be associated with active melanin production; their absence was demonstrated on senile white hair follicles.

Binding Sites↗
PubMed1991

Aberrant T cell regulation of IgE production in atopy.

Atopy is associated with elevated serum levels of allergen-specific immunoglobulin E (IgE). IgE production is preferentially induced by the T cell-derived lymphokine interleukin-4 (IL-4) and is suppressed by interferon and prostaglandins, of which interferon-gamma (IFN-gamma) is produced by T cells. We review our studies on the question of whether atopy is associated with CD4+ allergen-specific T cells with an unbalanced lymphokine production. We prepared panels of housedust mite (Dermatophagoides pteronyssinus)-specific T lymphocyte clones (TLC) from atopic and non-atopic individuals and found that TLC from housedust mite-allergic patients produced IL-4 but not IFN-gamma, whereas such TLC from a non-atopic individual produced IFN-gamma and only in some cases small amounts of IL-4. Candida albicans- and tetanus toxoid-specific TLC, established from one of the atopic donors, also produced IFN-gamma without IL-4, suggesting that the atopic state is characterized by a defective accumulation of IL-4-producing CD4+ T lymphocytes into the allergen-specific T cell repertoire.

Allergens↗
PubMed1991

Lack of efficacy of topical cyclosporin A in atopic dermatitis and allergic contact dermatitis.

Since oral cyclosporin A (CsA) has demonstrated its effectiveness in psoriasis and atopic dermatitis, efforts have been made to develop a topical CsA formulation, thus avoiding systemic adverse events. A limited number of publications are available on the use of topical CsA in allergic contact dermatitis and atopic dermatitis. Moreover the response rate of humans to topical CsA is about 50% or less. We now report our results with three new topical CsA formulations on allergic contact dermatitis and atopic dermatitis. No significant improvement was found in 16 atopic dermatitis patients and 7 allergic contact dermatitis (nickel sulphate) patients.

Administration, Cutaneous↗
PubMed1990

Evidence for compartmentalization of functional subsets of CD2+ T lymphocytes in atopic patients.

Lymphokine secretion profiles were studied of human allergen-specific CD4+ T lymphocyte clones (TLC). To this aim, panels of house dust mite Dermatophagoides pteronyssinus (Dp)-specific TLC were generated from two atopic Dp-allergic patients, suffering from severe atopic dermatitis (AD1) and allergic asthma (AD2), respectively, and from a non-atopic individual (NAD). From AD1 additional TLC were cloned specific for tetanus toxoid or Candida albicans, both Ag that were not relevant for the atopic state of this patient. Secretion of IL-2, IL-4, and IFN-gamma was determined after specific stimulation of these TLC, using autologous monocytes as APC. With respect to the production of IL-4 and IFN-gamma, clearly distinct profiles were observed. All Dp-specific TLC from both atopic donors produced IL-4 but not IFN-gamma, whereas the Dp-specific TLC from NAD, as well as the tetanus toxoid- and C. albicans-specific TLC from AD1, all produced IFN-gamma but not or small quantities of IL-4. Most TLC from all panels produced IL-2. These lymphokine profiles were consistent for at least 3 days and were neither dependent on the dose of allergen nor on the atopic or nonatopic state of the donor of APC. The functional consequence of these restricted lymphokine profiles was stressed by the observation that, whereas Dp-specific TLC from AD1 and AD2 supported in vitro IgE production, this support could be abrogated by a Dp-specific TLC from NAD. The present results suggest that CD4+ T lymphocytes that produce IL-4, but not IFN-gamma, occur in high frequencies in the allergen-specific T cell repertoires of atopic donors, which may have important implications for the pathomechanism of atopic disease.

Allergens↗