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Biomedical subjects

G Schuler

Publications and source records attributed to G Schuler.

At least 217 records · Page 12Linked to original sources
PubMed1994

Conjugates of dendritic cells and memory T lymphocytes from skin facilitate productive infection with HIV-1.

Experimentally, a productive infection with HIV-1 requires that virus be administered to T cells that are activated by mitogens. We describe a productive milieu for HIV-1 within the confines of normal skin that does not require standard stimuli. The milieu consists of dendritic cells and T cells that emigrate from skin and produce distinctive stable, nonproliferating conjugates. These conjugates, upon exposure to each of seven different HIV-1 isolates, begin to release high levels of virus progeny within 4 days. Numerous infected syncytia, comprised of both dendritic and T cells, rapidly develop. We propose that conjugates of dendritic cells and T cells, as found in the external linings of organs involved in sexual transmission of HIV-1, represent an important site for the productive phase of HIV-1 infection. Because the affected T cells carry the memory phenotype, this site additionally provides a mechanism for the chronic depletion of CD4+ memory cells in HIV-1 disease.

CD4-Positive T-Lymphocytes↗
PubMed1994

Proliferating dendritic cell progenitors in human blood.

CD34+ cells in human cord blood and marrow are known to give rise to dendritic cells (DC), as well as to other myeloid lineages. CD34+ cells are rare in adult blood, however, making it difficult to use CD34+ cells to ascertain if DC progenitors are present in the circulation and if blood can be a starting point to obtain large numbers of these immunostimulatory antigen-presenting cells for clinical studies. A systematic search for DC progenitors was therefore carried out in several contexts. In each case, we looked initially for the distinctive proliferating aggregates that were described previously in mice. In cord blood, it was only necessary to deplete erythroid progenitors, and add granulocyte/macrophage colony-stimulating factor (GM-CSF) together with tumor necrosis factor (TNF), to observe many aggregates and the production of typical DC progeny. In adult blood from patients receiving CSFs after chemotherapy for malignancy, GM-CSF and TNF likewise generated characteristic DCs from HLA-DR negative precursors. However, in adult blood from healthy donors, the above approaches only generated small DC aggregates which then seemed to become monocytes. When interleukin 4 was used to suppress monocyte development (Jansen, J. H., G.-J. H. M. Wientjens, W. E. Fibbe, R. Willemze, and H. C. Kluin-Nelemans. 1989. J. Exp. Med. 170:577.), the addition of GM-CSF led to the formation of large proliferating DC aggregates and within 5-7 d, many nonproliferating progeny, about 3-8 million cells per 40 ml of blood. The progeny had a characteristic morphology and surface composition (e.g., abundant HLA-DR and accessory molecules for cell-mediated immunity) and were potent stimulators of quiescent T cells. Therefore, large numbers of DCs can be mobilized by specific cytokines from progenitors in the blood stream. These relatively large numbers of DC progeny should facilitate future studies of their Fc epsilon RI and CD4 receptors, and their use in stimulating T cell-mediated resistance to viruses and tumors.

Animals↗
PubMed1994

Understanding the dendritic cell lineage through a study of cytokine receptors.

Dendritic cells form a system of antigen presenting cells that are specialized to stimulate T lymphocytes, including quiescent T cells. The lineage of dendritic cells is not fully characterized, although prior studies have shown that growth and differentiation are controlled by cytokines, particularly granulocyte/macrophage colony-stimulating factor (GM-CSF). To further elucidate the nature and control of the dendritic cell lineage, we have studied the expression of specific cytokine receptors. Sufficient numbers of dendritic cells were purified from spleen and skin to do quantitative binding studies with radiolabeled M-CSF, GM-CSF, and interleukin 1 (IL-1). To verify the nonlymphoid nature of dendritic cells, we made an initial search for rearrangements in T cell receptor and immunoglobulin genes and none were found. M-CSF binding sites, a property of mononuclear phagocytes, also were absent. In contrast, GM-CSF receptors were abundant on mature dendritic cells, with approximately 3,000 binding sites/cell with a single Kd of 500-1,000 pM. Substantial numbers of high affinity (< 100 pM) IL-1 binding sites were identified as well; cultured epidermal dendritic cells (i.e., epidermal Langerhans cells) had 500/cell and spleen dendritic cells approximately 70/cell. Cross-linking approaches showed the 80-kD species that is expected of high-affinity type 1 IL-1 receptor. Anti-type 1 IL-1 receptor (R) mAbs also visualized these receptors by flow cytometry on freshly isolated epidermal dendritic cells. These results provide new evidence that dendritic cells represent a differentiation pathway distinct from lymphocytes and monocytes. Together with recent findings on the effects of IL-1 and GM-CSF on epidermal dendritic cells in situ (see Results and Discussion), the data lead to a proposal whereby IL-1 signals IL-1R to upregulate GM-CSF receptors and thereby, the observed responsiveness of dendritic cells to GM-CSF for growth, viability, and function.

Animals↗
PubMed1994

Association between lipoprotein(a) and progression of coronary artery disease in middle-aged men.

The association between lipoprotein(a) (Lp[a]) and progression of coronary artery disease (CAD) compared with other serum lipids was evaluated in 104 patients with angiographically proven coronary atherosclerosis. Patients were randomized to either an intervention or a control group. The 12-month intervention program consisted of a low-fat diet and daily physical exercise. Patients in the control group received "usual care" by their private physician. Eighty-three patients (36 in the intervention and 47 in the control group) underwent repeat angiography after 1 year. Angiographically documented net regression was seen in 13 patients (8 in the intervention and 5 in the control group), no change was seen in 40 patients (21 in the intervention and 19 in the control group) and progression was noted in 30 patients (7 in the intervention and 23 in the control group). No correlation could be shown between Lp(a) and angiographically documented progression of the disease. In a multivariate analysis including metabolic variables, group assignment, age and smoking habits, only assignment to the intervention group (p = 0.0075) and a decrease in total cholesterol (p = 0.0167) were independently associated with the course of the disease. Patients with or without previous myocardial infarction (70 vs 34) did not differ in Lp(a) levels (median 9.15 vs 14.25 mg/dl). Patients with Lp(a) > 25 mg/dl were younger than patients with Lp(a) < or = 25 mg/dl (52 vs 55 years; p < 0.03), indicating a connection between Lp(a) and the development of premature CAD.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Disease↗
PubMed1994

[Low-fat diet and physical training in coronary heart disease. Long-term results of secondary prevention].

The long-term effect of a low-fat diet and physical training was investigated in 36 men (mean age 51 +/- 6 years) with coronary heart disease (one-vessel disease, n = 11; two vessel-disease: n = 18; three-vessel disease: n = 7). 18 patients (interventionist, group 1) undertook physical training within a coronary sport group (1 h twice weekly) and daily bicycle ergometry (30 min). They were held to a low-fat diet. In the remaining 18 patients (control, group 2), physical training and low-fat diet depended on own initiative after receiving advice. Over an observation period of 6 years total cholesterol concentration in the 17 patients of group 1 decreased significantly (243 +/- 33 vs. 219 +/- 28 mg/dl; P < 0.02). Physical performance in 12 patients (group 1) increased from 169 +/- 40 to 202 +/- 42 W in (P < 0.01). In contrast, total cholesterol increased slightly in group 2 (n = 16) from 245 +/- 31 at the beginning to 247 +/- 39 mg/dl (no significant change) at the end of the 6 years. Physical performance (n = 12) decreased slightly from 165 +/- 45 to 146 +/- 52 W (not significant). The difference between the two groups was significant after 6 years (P < 0.02 and P < 0.007, respectively). There seemed to be a tendency for progression of the coronary heart disease to be slower in the interventionist than the control group.

Body Mass Index↗
PubMed1994

Investigations on the use of C-21-steroids as precursors for placental oestrogen synthesis in the cow.

Cotyledonary homogenates from 220 and 270 day pregnant and term cows were incubated (NADPH- and NAD(+)-regenerating system) with 3H-pregnenolone and 3H-progesterone, respectively. Identification of metabolites was based on separation on HPLC and the respective retention times. On days 220/270 the major metabolite formed after incubation with 3H-pregnenolone was progesterone, followed by 17 alpha-hydroxyprogesterone and dehydroepiandrosterone/17 alpha-hydroxypregnenolone; the formation of estrone was low (up to 6%), while it was the major metabolite after incubation of pregnenolone with term placenta. At all stages of pregnancy investigated, the only metabolite found after incubation with 3H-progesterone was 17 alpha-hydroxyprogesterone. These data provide evidence that 17 alpha-hydroxyprogesterone is the endpoint of steroid biosynthesis in the bovine placenta along the delta 4-route and that oestrogen synthesis follows the delta 5-pathway. Based on the high activity of 3 beta-hydroxysteroiddehydrogenase/delta 5/4-isomerase also found on days 220/270, the key enzyme allowing for placental oestrogen synthesis in the cow seems to be cytochrome P450c17 alpha. Thus the situation in the cow is similar to that in the sheep and the increased turnover of pregnenolone into estrone may explain the decrease of placental progesterone production in the cow towards the end of gestation.

Animals↗
PubMed1994

Verapamil treatment after coronary angioplasty in patients at high risk of recurrent stenosis.

OBJECTIVE: To evaluate the efficacy of high-dose verapamil treatment (240 mg twice daily) in the prevention of angiographic restenosis after primary successful coronary angioplasty in patients at high risk of recurrent obstruction. DESIGN: A placebo controlled, double blind trial in which patients with stable angina pectoris and patients with unstable angina or non-Q wave infarction treated with 330 mg aspirin and 75 mg dipyridamole twice daily were randomised to a verapamil group or a control group. Follow up angiography was performed 6 months after angioplasty or sooner if signs of recurrent ischaemia developed. SETTING: University department of cardiology. PATIENTS: 196 consecutive patients undergoing coronary angioplasty from the beginning of April 1987 to the end of March 1989 and meeting the selection criteria that included the presence of at least one of six predefined risk factors for restenosis. At the time of coronary angioplasty 113 patients had unstable angina or non-Q wave infarction and 83 had stable angina pectoris. RESULTS: In 89 (91%) patients in the verapamil group and in 83 (85%) control patients follow up angiograms were available. The restenosis rate was lower in the verapamil group (48.3%) than in the placebo group (62.7%) (odds ratio 0.56, 95% confidence interval (CI) 0.303 to 1.025 p = 0.059). Of the 172 patients in whom follow up angiograms were available, 24 (13 taking verapamil and 11 taking placebo) did not comply with the trial for more than 40 (34) days (mean (1 SD)). For the remaining 148 patients the restenosis rate was 47.4% in the verapamil group and 63.9% in the placebo group (odds ratio 0.52, 95% CI 0.271 to 0.993, p = 0.046). In the 97 patients with unstable angina or non-Q wave infarction the restenosis rate was not significantly influenced by verapamil (55.8% with verapamil v 62.2% with placebo, odds ratio 0.77, 95% CI 0.339 to 1.728, p = 0.520). In the 75 patients with stable angina pectoris the restenosis rate dropped from 63.2% with placebo to 37.8% with verapamil (odds ratio 0.36, 95% CI 0.137 to 0.917, p = 0.038). CONCLUSION: The observed beneficial effect of high-dose verapamil treatment on the angiographic restenosis rate in patients with stable angina pectoris and at increased risk of recurrent obstruction requires confirmation in further prospective studies.

Aged↗
PubMed1994

[Antibiotic therapy of infectious endocarditis (when, with what drug, how long?].

The aim of antibiotic therapy in bacterial endocarditis is to sterilize infected cardiac structures and vegetations. Pathogenic organisms are present in great numbers within vegetations and abscess-formations. They exist in a state of reduced metabolic activity so that they are able to tolerate even therapeutic levels of bactericidal antibiotic concentrations. Because vegetations are normally devoid of blood vessels, impregnation with antibiotic agents is poor. Effective therapy is greatly improved by identification of the pathogenic organism involved. With very few exceptions isolation is possible prior to initiation of antibiotic therapy. In acute cases with signs of septicemia, however, therapy cannot await results of bacterial testing. In these patients selection of antibiotic agents is based on associated evidence such as the presence of a prosthetic heart valve or intravenous drug addiction. Once the pathogen has been identified antibacterial therapy should be tailored according to the test results. Bactericidal antibiotics should always be preferred over bacteriostatic agents; in many cases adequate bactericidal levels can only be achieved by combining various agents, such as ampicillin and gentamycin for treatment of enterococcal endocarditis. Dosing intervals must take into account the resulting trough levels, which should always exceed the minimal inhibitory concentrations for a specific bacterial strain. In cases with inadequate control of infection, congestive heart failure resulting from valve dysfunction, and abscess formation, surgery as the only means of eradicating the infection and restoring cardiac performance should not be delayed.

Anti-Bacterial Agents↗
PubMed1993

[Successful lysis therapy in acute unilateral renal vein thrombosis].

A nephrotic syndrome developed in a 50-year-old man who, because of rheumatoid arthritis for the last three years, had been receiving gold therapy (30-50 mg sodium aurothiomalate weekly for 10 months). Treatment for the nephrotic syndrome was initiated with 100 mg prednisone daily. Ten days later he complained of severe pain in his right flank and haematuria was noted. Serum creatinine concentration increased from 1.0 to 1.8 mg/dl, while creatinine clearance fell to 62 ml/min. Computed tomography demonstrated significant enlargement of the right kidney and a thrombus in the right renal vein which extended cranial into the inferior vena cava. High dosage infusion of urokinase (4.5-7.5 mill. IU daily for nine days) achieved complete lysis of the thrombus. The creatinine concentration fell to 1.1 mg/dl, while creatinine clearance rose to 104 ml/min. On the 5th day the right kidney had 25% of total function, several days later 40%.--This case illustrates that, as long as there are no contraindications, adequately high doses of urokinase can be appropriate treatment of acute renal vein thrombosis associated with the nephrotic syndrome.

Acute Disease↗
PubMed1993

Interleukin 7 is produced by murine and human keratinocytes.

Interleukin 7 (IL-7) was originally identified as a growth factor for B cell progenitors, and subsequently has been shown to exert proliferative effects on T cell progenitors and mature peripheral T cells as well. Constitutive IL-7 mRNA expression so far had been demonstrated in bone marrow stromal cell lines, thymus, spleen, and among nonlymphoid tissues in liver and kidney. Here we show that both murine and human keratinocytes express IL-7 mRNA and release IL-7 protein in biologically relevant amounts. The physiological or pathological relevance of keratinocyte-derived IL-7 is presently unknown. Our finding that keratinocytes can produce IL-7 in concert with reports that IL-7 is a growth factor for in vivo primed antigen-specific T cells, as well as for T lymphoma cells suggests, however, that keratinocyte-derived IL-7 is important in the pathogenesis of inflammatory skin diseases and cutaneous T cell lymphoma.

Animals↗
PubMed1993

Renal proximal and distal tubular function is attenuated in diabetes mellitus type 1 as determined by the renal excretion of alpha 1-microglobulin and Tamm-Horsfall protein.

Diabetic nephropathy is usually characterized by glomerular dysfunction; the view that tubular damage occurs as a consequence, however, has been disputed. To verify this hypothesis we compared glomerular with proximal and distal tubular parameters in 62 patients with diabetes mellitus type I. The duration of disease ranged between 0 and 39 years and the glomerular, proximal tubular, and distal tubular parameters were investigated in 24-h urine samples. Excretion of albumin as a marker of the glomerulum, alpha 1-microglobulin and N-acetyl-beta-D-glucosaminidase as parameters of proximal tubule, and Tamm-Horsfall protein as parameter of distal tubule were determined by sensitive enzyme-linked immunosorbent assays. Patients were divided into five groups (D1-D5) according to the duration of diabetes as follows: D1, less than 1 year; D2, 1-4 years; D3, 5-9 years; D4, 10-14 years; D5, longer than 14 years. Healthy individuals (n = 61) aged 3-42 years served as controls. Significantly increased excretion of proximal tubular parameters were found in early course while albumin excretion was still in the normal range. In addition, proximal tubular alpha 1-microglobulin showed an increase during the course of diabetes duration, probably indicating an early proximal tubular impairment. Distal tubular Tamm-Horsfall protein showed increasing excretion in D1-D4, which may reflect disturbance of the thick ascending loop of Henle. Our results therefore stress the importance of tubular parameters such as alpha 1-microglobulin during early diabetes mellitus type I since they may serve as early markers of renal dysfunction and may precede albumin excretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylglucosaminidase↗
PubMed1993

Various intensities of leisure time physical activity in patients with coronary artery disease: effects on cardiorespiratory fitness and progression of coronary atherosclerotic lesions.

OBJECTIVES: This study was designed to define the effect of different levels of leisure time physical activity on cardiorespiratory fitness and progression of coronary atherosclerotic lesions in unselected patients with coronary artery disease. BACKGROUND: It has been shown in various studies that regression of coronary atherosclerotic lesions can be achieved by means of lipid-lowering drugs, reduction of fat consumption and physical exercise. METHODS: Patients were prospectively randomized either to an intervention group (n = 29) participating in regular physical exercise or to a control group (n = 33) receiving usual care. Energy expenditure in leisure time physical activity was estimated from standardized questionnaires and from participation in group exercise sessions. After 12 months of participation, repeat coronary angiography was performed; coronary lesions were measured by digital image processing. RESULTS: After 1 year, patients in the intervention group achieved an increase in oxygen uptake at a ventilatory threshold of 7% (p < 0.001) and peak exercise of 14% (p < 0.05), whereas a significant decrease was observed in patients in the control group. To achieve significant improvement in cardiorespiratory fitness, approximately 1,400 kcal/week had to be expended in the form of leisure time physical activity (p < 0.001). The mean energy expended in such activity was 1,876 +/- 163 kcal/week in the intervention group and 1,187 +/- 97 kcal/week in the control group (p < 0.001). In the intervention group, regression of coronary artery disease was noted in 8 patients (28%), progression of disease in 3 (10%) and no change in coronary morphology in 18 (62%). In contrast, coronary artery disease progressed at a significantly faster rate in patients in the control group (progression in 45%, no change in 49% and regression in 6%) (p < 0.001 vs. intervention). When the two groups were combined, the lowest level of leisure time physical activity was noted in patients with progression of disease (1,022 +/- 142 kcal/week) as opposed to patients with no change (1,533 +/- 122 kcal/week) or regression of disease (2,204 +/- 237 kcal/week) (p < 0.005). CONCLUSIONS: Measurable improvement in cardiorespiratory fitness requires approximately 1,400 kcal/week of leisure time physical activity; higher work loads are necessary to halt progression of coronary atherosclerotic lesions (1,533 +/- 122 kcal/week), whereas regression of coronary lesions is observed only in patients expending an average of 2,200 kcal/week in leisure time physical activity, amounting to approximately 5 to 6 h/week of regular physical exercise.

Coronary Angiography↗
PubMed1993

Hemopoietic stem cell inhibitor (SCI/MIP-1 alpha) also inhibits clonogenic epidermal keratinocyte proliferation.

The maintenance and regulation of continuously renewing tissues is ultimately controlled at the level of stem-cell proliferation. We have recently identified a reversible inhibitor of hemopoietic stem-cell proliferation (stem-cell inhibitor [SCI]), which is identical to the macrophage inflammatory protein, MIP-1 alpha, a 69-amino-acid heparin-binding cytokine. To test the cell/tissue specificity of the inhibition of proliferation by SCI/MIP-1 alpha, we have investigated its activity on epidermal keratinocytes, the principal cell type of another continuously renewing tissue. Here we show that SCI/MIP-1 alpha inhibits the proliferation of epidermal keratinocytes in vitro and that the MIP-1 alpha mRNA is present in epidermal Langerhans cells but not in keratinocytes. This suggests an important growth regulatory function for SCI/MIP-1 alpha in keratopoiesis, as well as hemopoiesis, and may also indicate a novel role for the epidermal Langerhans cell. As SCI/MIP-1 alpha can inhibit the proliferation of embryologically distinct precursor cells, this raises the possibility that it may also function in a number of other tissues.

Animals↗
PubMed1993

Human and murine dermis contain dendritic cells. Isolation by means of a novel method and phenotypical and functional characterization.

Dendritic cells (DC) comprise a system of cells in lymphoid and nonlymphoid organs that are specialized to present antigens and to initiate primary T cell responses. The Langerhans cell of the epidermis is used as a prototype for studies of DC in the skin. We have characterized a population of DC in human dermis, one of the first examples of these cells in nonlymphoid organs other than epidermis. To identify their distinct functions and phenotype, we relied upon the preparation of enriched populations that emigrate from organ explants of dermis. The dermal cells have the following key features of mature DC: (a) sheet-like processes, or veils, that are constantly moving; (b) very high levels of surface MHC products; (c) absence of markers for macrophages, lymphocytes, and endothelium; (d) substantial expression of adhesion/costimulatory molecules such as CD11/CD18, CD54 (ICAM-1), B7/BB1, CD40; and (e) powerful stimulatory function for resting T cells. Dermal DC are fully comparable to epidermis-derived DC, except for the lack of Birbeck granules, lower levels of CD1a, and higher levels of CD36. DC were also detected in explants of mouse dermis. We conclude that cutaneous DC include both epidermal and dermal components, and suggest that other human nonlymphoid tissues may also serve as sources of typical immunostimulatory DC.

Animals↗
PubMed1993

Identification of macrophages and dendritic cells in the osteopetrotic (op/op) mouse.

We used a panel of monoclonal antibodies and immunocytochemistry to identify macrophages and dendritic cells in mice that are deficient in macrophage colony stimulating factor (M-CSF or CSF-1) because of the recessive osteopetrotic (op/op) mutation. Prior work had shown that osteopetrosis is associated with a lack of osteoclasts, phagocytic cells required for remodelling in bone. Additional macrophage populations proved to be very M-CSF dependent. op/op mice had few and sometimes no peritoneal cavity phagocytes, splenic marginal zone metallophils, and lymph node subcapsular sinus macrophages. Other populations, however, reached substantial levels in the absence of M-CSF, including phagocytes in the thymic cortex, splenic red pulp, lymph node medulla, intestinal lamina propria, liver (Kupffer cells), lung (alveolar macrophages) and brain (microglia). Dendritic cells, which are specialized accessory cells for T-dependent immune responses and tolerance, were readily identified in skin and in the T-dependent regions of spleen, lymph node and Peyer's patch. The identification of dendritic cells utilized antibodies to MHC class II products and four different antigens that are primarily expressed by these accessory cells. Our findings indicate that only a few macrophage populations are critically dependent upon M-CSF in vivo. With respect to dendritic cells, the data are consistent with prior in vitro work where it was noted that GM-CSF but not M-CSF supported dendritic cell viability, function and growth.

Animals↗
PubMed1993

[Slowing the progression and regression of the basic arteriosclerotic process].

UNLABELLED: If patients with coronary artery disease are followed by "usual care" nearly half of them will experience significant progression of their disease within five years. Therefore, it is justified to develop interventions in order to retard the rate of progression and reduce the number of clinical events. In relevant studies published up to this date two different strategies were applied, first, reduction of risk factors by low fat diet, physical exercise, lipid lowering agents or partial ileal bypass; second, inhibition of atherogenesis by application of calcium blocking agents. The effect on progression of coronary artery disease was assessed by digital angiography in the majority of studies; without exception a positive effect was noted in all of them. In the calcium blocker studies this effect, however, was limited to new or minimal lesions. The magnitude of morphological difference between intervention and control groups ranged below 0.5 mm and thus approached the long term variability of quantitative coronary angiography. The frequency of clinical events was reduced in only two studies, whereas they were increased in four intervention groups. CONCLUSIONS: Reduction of risk factors or application of calcium blockers are capable of retarding progression of coronary artery disease; predominant regression, however, seems to be unattainable. The frequency of clinical events is determined by additional factors other than morphologic changes.

Calcium Channel Blockers↗
PubMed1993

[Contact allergy].

Following epicutaneous application of a potential contact sensitizing agent (hapten) allergic contact dermatitis results if sensitizing rather than tolerizing signals become dominant. Whereas downregulatory signals are poorly defined it has become clear that epidermal Langerhans cells play an important role in the induction of contact allergy. The current hypothesis is that in vivo, subsequent to deposition of antigen, resident Langerhans cells mature into potent immunostimulatory, antigen-carrying dendritic cells which migrate via the afferent lymphatics and after their arrival in the draining lymph node select and sensitize clones of antigen-specific T-cells from the circulating pool. These T-cells produce Interleukin-2 and Interferon-gamma, and, thus, constitute so-called type 1 helper T-cells (Th 1). Recent progress has shed light on some major unknowns in this sequence of events such as regulatory influences, nature of the T-cell receptor ligand, and extravasation of T-cells at the site of hapten deposition. For example, epidermal cell-derived cytokines seem important for initiation (Interleukin-1) and sustenance (GM-CSF) of the induction phase. Hapten-specific T-cells seem to see hapten molecules bound to peptides in the groove of the MHC molecules, and specific endothelial adhesion molecules (ELAM-1) mediate extravasation of skin-homing T-cells that carry a specific ligand (CLA). The recent development of techniques to grow murine as well as human Langerhans cells and dendritic cells in large numbers will allow researchers to further elucidate the pathogenesis of contact hypersensitivity and will ultimately lead to the design of novel strategies for immodulation and tolerance induction.

Allergens↗