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1.
Rheumatol Int ; 32(5): 1121-33, 2012 May.
Article in English | MEDLINE | ID: mdl-22083610

ABSTRACT

Uveitis in juvenile idiopathic arthritis (JIA) is frequently associated with the development of complications and visual loss. Topical corticosteroids are the first-choice therapy, and immunosuppression is commonly used. However, treatment has not been standardized. Representatives from the German Ophthalmological Society, Society for Childhood and Adolescent Rheumatology, and the German Society for Rheumatology reached consensus on a standardized treatment strategy according to disease severity in the individual patient. The recommendations were based on a systematic literature analysis in MEDLINE and consensus expert meetings. Evidence and recommendations were graded, and an algorithm for anti-inflammatory treatment and final statements confirmed in a Delphi method. An interdisciplinary, evidence-based treatment guideline for JIA uveitis is presented.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Arthritis, Juvenile/complications , Evidence-Based Medicine/standards , Ophthalmology/standards , Rheumatology/standards , Uveitis/drug therapy , Adolescent , Algorithms , Anti-Inflammatory Agents/adverse effects , Arthritis, Juvenile/immunology , Child , Cooperative Behavior , Delphi Technique , Germany , Humans , Interdisciplinary Communication , Patient Care Team , Recurrence , Treatment Outcome , Uveitis/diagnosis , Uveitis/etiology , Uveitis/immunology
2.
Klin Padiatr ; 223(6): 386-94, 2011 Nov.
Article in German | MEDLINE | ID: mdl-22012606

ABSTRACT

BACKGROUND: Treatment of Juvenile Idiopathic Arthritis (JIA) has improved quality of life in children and adolescents with JIA. Standardisation of care offers the chance to improve the quality of care of those patients. New studies have been published after completion of our last treatment guideline (2007). An updated consensus process is mandatory. METHODS: A systematic literature analysis in PUBMED (key words: juvenile idiopathic (rheumatoid) arthritis, therapy; limits: humans, published in the last 3 years, all child 0-18 years, clinical trial) revealed 17 relevant studies. Studies relating to diagnosis of JIA, Uveitis, vaccination, transition were excluded. Representatives nominated by scientific societies and organisations were invited to consensus conferences which were hosted by a professional moderator. The following societies were invited: Berufsverband der Kinder- und Jugendärzte (BVKJ), Deutsche Gesellschaft für Kinder- und Jugendmedizin (DGKJ), Deutsche Gesellschaft für Rheumatologie (DGRh), Deutsche Ophthalmologische Gesellschaft (DOG), Deutsche Rheuma-Liga Bundesverband, Verein zur Förderung und Unterstützung rheumatologisch erkrankter Kinder und deren Eltern, Vereinigung für Kinderorthopädie, Zentraler Verband der Physiotherapeuten und Krankengymnasten (ZVK). Consensus conferences were each attended by more than 95% of the nominated representatives. Consensus statements were confirmed by nominal group technique and Delphi method. RESULTS AND CONCLUSION: Updated consensus statements regarding drug therapy, symptomatic and surgical management of JIA were compiled and judged strictly by the criteria of Evidence-Based Medicine (EBM).


Subject(s)
Arthritis, Juvenile/therapy , Cooperative Behavior , Evidence-Based Medicine , Interdisciplinary Communication , Adolescent , Anti-Inflammatory Agents/therapeutic use , Antirheumatic Agents/therapeutic use , Arthritis, Juvenile/diagnosis , Biological Products/therapeutic use , Child , Child, Preschool , Combined Modality Therapy , Germany , Glucocorticoids/therapeutic use , Humans , Immunosuppressive Agents/therapeutic use , Infant , Occupational Therapy , Physical Therapy Modalities
3.
Rheumatol Int ; 31(12): 1639-43, 2011 Dec.
Article in English | MEDLINE | ID: mdl-20013264

ABSTRACT

To report on the differential diagnosis of lyme arthritis and synovial hemangioma due to similar clinical and radiological signs and symptoms. A 15-year-old boy presented at the age of 9 with recurrent rather painless swelling of the right knee. Altogether four episodes lasting for 1-2 weeks each occurred over a period of 18 months before medical advice was sought. Physical examination revealed only a slightly limited range of motion. Living in an endemic area of borreliosis, he reported a tick bite 6 months prior to onset of his symptoms with erythema migrans and was treated for 10 days with amoxicillin. Serology revealed two positive unspecific bands in IgG immunoblot (p41 and 66) with slight positivity for ELISA. Ultrasound revealed synovial thickening and increased fluid. Despite the weak positive serology a diagnosis of lyme arthritis could not be excluded and intravenous antibiotic treatment with ceftriaxone was started. After two further relapses antiinflammatory therapy including intraarticular steroids were introduced with no long lasting effect. A chronical disease developed with alternate periods of swelling and almost complete remission. Ultrasound as well as MRI demonstrated ongoing signs of synovitis, therefore after further progression, a diagnostic arthroscopy was performed showing an inconspicuous knee joint. A second MRI showed focal suprapatellar enhancement and was followed by open arthrotomy revealing a histopathological proven synovial cavernous juxtaarticular hemangioma. To our knowledge, the differential diagnosis of lyme arthritis and synovial hemangioma has not yet been reported despite obvious clinical similarities. In conclusion, in children and adolescents synovial hemangioma has to be considered in differential diagnosis of recurrent knee swelling. Early diagnosis is important to prevent prolonged suffering from chronic joint swelling with probable joint damages, unnecessary treatment procedures and as well school and sports absenteeism.


Subject(s)
Hemangioma/pathology , Joint Diseases/diagnosis , Knee/pathology , Lyme Disease/pathology , Synovial Membrane/pathology , Adolescent , Anti-Bacterial Agents/therapeutic use , Arthroscopy , Ceftriaxone/therapeutic use , Diagnosis, Differential , Hemangioma/drug therapy , Humans , Joint Diseases/pathology , Knee/diagnostic imaging , Lyme Disease/drug therapy , Magnetic Resonance Imaging , Male , Range of Motion, Articular , Synovitis/pathology , Ultrasonography
4.
Z Rheumatol ; 69(6): 561-7, 2010 Aug.
Article in German | MEDLINE | ID: mdl-20174926

ABSTRACT

TNF inhibitors and other biologicals have greatly expanded the therapeutic options for juvenile idiopathic arthritis (JIA). While the efficacy of etanercept and adalimumab has been proven in randomized controlled clinical trials, their long-term safety remains the subject of ongoing investigations. Reports of leukaemia and tumours in children and adolescents treated with etanercept, infliximab and adalimumab have raised questions about an increased risk for malignancies, with lymphoma accounting for the largest group at 50% of all 48 malignancies reported by the FDA.Consequently, TNF inhibitors should be indicated under careful consideration of individual risk factors, such as increased family occurrence of malignancies, or pre-treatment with carcinogenic substances such as cyclophosphamide. This is particularly true for non-approved substances, and non-approved indications, and for combination therapy of TNF inhibitors with immunosuppressive drugs. On the other hand, however, treatment should not be stopped or started in any patient in whom treatment is necessary due to the current knowledge. Adequate patient information, surveillance and documentation of treatment in the registry of the GKJR is strongly recommended.


Subject(s)
Adverse Drug Reaction Reporting Systems , Arthritis, Juvenile/drug therapy , Biological Products/adverse effects , Neoplasms/chemically induced , Societies, Medical , Tumor Necrosis Factor-alpha/antagonists & inhibitors , United States Food and Drug Administration , Adolescent , Adult , Biological Products/therapeutic use , Child , Humans , Leukemia/chemically induced , Lymphoma/chemically induced , Off-Label Use , Treatment Outcome , United States , Young Adult
6.
Eur J Pediatr ; 168(1): 1-9, 2009 Jan.
Article in English | MEDLINE | ID: mdl-18830624

ABSTRACT

OBJECTIVES: The objectives of this study were to analyse the literature on Sweet's syndrome in childhood focussing on associated diseases and to suggest possible screening procedures for this group of patients. Furthermore, two new patients with Sweet's syndrome are reported. METHODS: A literature search was performed on Pub med using search terms "sweet* syndrome*" and neutrophil* dermatos*. Patients were subdivided into the following groups: classic/idiopathic, paraneoplastic, and parainflammatory Sweet's syndrome. RESULTS: The literature search revealed 64 patients (including our two patients) who were diagnosed with Sweet's syndrome in childhood and adolescence; 27 (42%) patients were categorized as "classic/idiopathic Sweet's syndrome". In 37 patients (58%) chronic associated diseases were reported. Out of these, 21 (33%) patients were categorized as "parainflammatory Sweet's syndrome" including chronic recurrent multifocal osteomyelitis, vasculitis with aortitis, recurrent infections due to immunodeficiencies, arthritis, and systemic lupus erythematosus. Sixteen (25%) patients were categorized as "paraneoplastic Sweet's syndrome" comprising both malignant and premalignant diseases like leukemia, aplastic anaemia, and Fanconi anaemia. As all five (8%) patients treated with drugs (granulocyte-colony stimulating factor, retinoid acid) suffered from malignant, premalignant, or parainflammatory diseases, these patients were categorized according to the underlying disease. Two new children with Sweet's syndrome and associated diseases are presented here, one of them suffering from recurrent infections and trisomy 21, while the other was diagnosed with CNS vasculitis 5(1/2) years after the primary diagnosis. CONCLUSIONS: Sweet's syndrome should be considered in differential diagnosis of prolonged fever with cutaneous involvement. As most cases of pediatric Sweet's syndrome are associated with other diseases we suggest careful screening and monitoring of these patients especially concerning malignant/premalignant diseases, immunodeficiencies, cardiovascular involvement, autoimmune diseases, and drug associations.


Subject(s)
Fever/diagnosis , Fever/metabolism , Mass Screening/methods , Neutrophils/metabolism , Skin Diseases/diagnosis , Skin Diseases/metabolism , Sweet Syndrome/epidemiology , Sweet Syndrome/physiopathology , Acute Disease , Adolescent , Child , Child, Preschool , Diagnosis, Differential , Female , Humans , Immunoglobulins/blood , Infant , Male , Neutropenia/diagnosis , Neutrophils/pathology , Severity of Illness Index , Skin Diseases/pathology , Sweet Syndrome/diagnosis
7.
Klin Padiatr ; 220(1): 47-52, 2008.
Article in German | MEDLINE | ID: mdl-18095254

ABSTRACT

Henoch-Schoenlein Purpura (PSH) is the most frequent vasculitis in childhood. Skin, bowel and joints are characteristically involved. Although renal manifestations are common PSH-nephritis is infrequent but characterized by a poor prognosis. In autumn 2005 diagnosis and treatment were discussed at the 8th consensus meeting in Wörlitz. These results are summarized.


Subject(s)
IgA Vasculitis , Adolescent , Age Factors , Biopsy , Child , Consensus Development Conferences as Topic , Diagnosis, Differential , Follow-Up Studies , Germany , Hospitalization , Humans , IgA Vasculitis/complications , IgA Vasculitis/diagnosis , IgA Vasculitis/diagnostic imaging , IgA Vasculitis/drug therapy , IgA Vasculitis/pathology , IgA Vasculitis/therapy , Infant , Infant, Newborn , Kidney/pathology , Nephritis/diagnosis , Nephritis/etiology , Prognosis , Radiography , Skin/pathology , Time Factors , Ultrasonography
8.
Gait Posture ; 25(4): 615-9, 2007 Apr.
Article in English | MEDLINE | ID: mdl-16905321

ABSTRACT

BACKGROUND: The knowledge of limb segment masses is critical for the calculation of joint torques. Several methods for segment mass estimation have been described in the literature. They are either inaccurate or not applicable to the limb segments of children. Therefore, we developed a new cylinder brick model (CBM) to estimate segment mass in children. METHODS: The aim of this study was to compare CBM and a model based on a polynomial regression equation (PRE) to volume measurement obtained by the water displacement method (WDM). We examined forearms, hands, lower legs, and feet of 121 children using CBM, PRE, and WDM. The differences between CBM and WDM or PRE and WDM were calculated and compared using a Bland-Altman plot of differences. FINDINGS: Absolute limb segment mass measured by WDM ranged from 0.16+/-0.04 kg for hands in girls 5-6 years old, up to 2.72+/-1.03 kg for legs in girls 11-12 years old. The differences of normalised segment masses ranged from 0.0002+/-0.0021 to 0.0011+/-0.0036 for CBM-WDM and from 0.0023+/-0.0041 to 0.0127+/-0.036 for PRE-WDM (values are mean+/-2 S.D.). The CBM showed better agreement with WDM than PRE for all limb segments in girls and boys. INTERPRETATION: CBM is accurate and superior to PRE for the estimation of individual limb segment mass of children. Therefore, CBM is a practical and useful tool for the analysis of kinetic parameters and the calculation of resulting forces to assess joint functionality in children.


Subject(s)
Anthropometry/methods , Extremities/anatomy & histology , Models, Biological , Adolescent , Child , Child, Preschool , Extremities/physiology , Female , Humans , Male , Regression Analysis , Sex Characteristics , Torque
9.
Z Rheumatol ; 65(4): 315-22, 324-6, 2006 Jul.
Article in German | MEDLINE | ID: mdl-16710651

ABSTRACT

Rheumatic diseases in childhood and adolescence differ from those of adulthood according to type, manifestation, treatment and course. A specialized therapy, starting as early as possible, improves the prognosis, can prevent long-term damage and saves the costs of long-term care. Only a specialized pediatric care system can guarantee optimum quality of the processes involved and the results for rheumatology in childhood and adolescence within a global financial system. This requires adequate structural quality of the specialized clinics and departments for pediatric rheumatology. The management of rheumatic diseases in childhood and adolescence is comprehensive and requires a multidisciplinary, specialized and engaged team which can cover the whole spectrum of rheumatic diseases with their various age-dependent aspects. In order to guarantee an adequate, cost-efficient routine, a specialized center which concentrates on inpatient care should treat at least 300 patients with pediatric rheumatic diseases per year. The diagnoses should be divided among the various disease categories with at least 70% of them involving inflammatory rheumatic diseases. For the inpatient care of small children, an accompanying person (parent) is necessary, requiring adequate structures and services. Patient rooms as well as diagnostic (radiography, sonography, etc.) and therapeutic services (physiotherapy, occupational therapy, pool, etc.) must be adequate for small children and school children as well as adolescents. Suitable mother-child units must also be provided and a school for patients is required within the clinic. A pediatric rheumatologist must be available 24 h a day, and it must be possible to reach other specialists within a short time. For painful therapeutic procedures, age-appropriate pain management is obligatory. A continuous adjustment of these recommendations to changing conditions in health politics is intended.


Subject(s)
Hospital Departments/standards , Hospital Design and Construction/statistics & numerical data , Hospitals, Pediatric/standards , Hospitals, Special/standards , Patient Care Team/standards , Quality Assurance, Health Care/standards , Rheumatic Diseases/therapy , Adolescent , Child , Cost-Benefit Analysis/standards , Early Diagnosis , Germany , Health Services Needs and Demand/standards , Humans , Outcome Assessment, Health Care/standards , Rheumatic Diseases/diagnosis , Specialization/standards
10.
Rheumatology (Oxford) ; 45(9): 1125-8, 2006 Sep.
Article in English | MEDLINE | ID: mdl-16510525

ABSTRACT

OBJECTIVE: In children with juvenile idiopathic arthritis (JIA), alterations of the skeletal system have been described. The aim of this cross-sectional study was to evaluate a phalangeal bone ultrasound device in the assessment of the skeletal status in children with active JIA. METHODS: In 49 children with oligoarticular, polyarticular or systemic JIA, the speed of an ultrasound signal (Ad-SOS) through the phalanges of the dominant hand was measured using the Igea 1200. RESULTS: Children in all subgroups were significantly smaller than those in the reference population, but there were no significant deficits in Ad-SOS. The finger width was reduced only in patients with polyarticular JIA. The Ad-SOS correlated highly with height, but no correlation between the finger width and Ad-SOS, and no correlation between the standard deviation scores of body height and Ad-SOS were seen. CONCLUSIONS: Phalangeal ultrasound is strongly dependent on body and therefore bone size, but other parameters of bone and soft tissues influence the measurements as well. It is not possible to differentiate as to which extent the various components of bone and soft tissue influence the measurement results. Ultrasound might therefore be of limited value in the assessment or screening of the skeletal system in children with JIA.


Subject(s)
Arthritis, Juvenile/diagnostic imaging , Finger Phalanges/diagnostic imaging , Adolescent , Body Height , Child , Child, Preschool , Cross-Sectional Studies , Female , Humans , Male , Predictive Value of Tests , Statistics, Nonparametric , Tomography, X-Ray Computed , Ultrasonography
11.
Clin Exp Immunol ; 137(3): 578-83, 2004 Sep.
Article in English | MEDLINE | ID: mdl-15320909

ABSTRACT

Common variable immunodeficiency (CVID) is a heterogeneous immunodeficiency that is accompanied by granulomatous lesions in 5-10% of cases. Why some patients develop granulomatous disease remains unclear. Here we describe a 12-year-old previously healthy girl who presented with pancytopenia and granulomatous lymphoproliferation subsequent to infection with Toxoplasma gondii. Loosely arranged non-fibrosing granulomas were observed in the liver, lymph nodes and lung, but no Toxoplasma tachyzoites could be demonstrated and polymerase chain reaction (PCR) and culture were negative for Toxoplasma and a wide range of other pathogens. While the patient had a normal peripheral B cell status at presentation, the development of CVID could be observed during the following months, leading to a loss of memory B cells. This was accompanied by an increasingly activated CD4(+) T cell compartment and high serum levels of angiotensin-converting enzyme (ACE), tumour necrosis factor (TNF) and sCD25. Steroid therapy reduced pancytopenia, granulomatous lymphoproliferation and cytokine elevations, but did not improve the B cell status. This is the first report of an association of Toxoplasma infection with granulomatous CVID and provides one of the rare examples where the onset of CVID could be documented subsequent to an infectious disease.


Subject(s)
Common Variable Immunodeficiency/parasitology , Lymphomatoid Granulomatosis/parasitology , Toxoplasmosis/immunology , Acute Disease , B-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/immunology , Child , Common Variable Immunodeficiency/immunology , Female , Humans , Immunohistochemistry , Liver/immunology , Lung/immunology , Lymph Nodes/immunology , Lymphocyte Activation , Lymphocyte Count , Lymphomatoid Granulomatosis/immunology
12.
Clin Exp Rheumatol ; 21(2): 257-62, 2003.
Article in English | MEDLINE | ID: mdl-12747287

ABSTRACT

OBJECTIVE: In the oligoarticular subgroup of juvenile idiopathic arthritis, a strong association has been found with the expression of human leukocyte antigen class II molecules HLA-DQA1 *0401-DQB1*0402 and DQA1*0501-DQB1*0301, whereas DQA1*0501-DQB1*0201 is neutral and DQA1 *0201-DQB1*0201 protective. A presentation of different peptides by these DQ alleles would support their role in the disease process. METHODS: Using a synthetic nonapeptide library, a peptide binding motif was determined for the associated DQA1*0501-DQB1*0301 molecule and compared to the neutral and the protective DQ molecules. RESULTS: A differential motif for the three molecules could be deduced, suggesting that peptides preferentially binding to the associated vs. the neutral/protective DQ-molecules are mutually exclusive. CONCLUSION: These results imply a role for differential peptide presentation in the pathogenesis of oligoarthritic JIA. The search for peptides initiating the disease process might be facilitated which could then lead to therapeutical interventions.


Subject(s)
Arthritis, Juvenile/metabolism , HLA-DQ Antigens/immunology , Peptide Library , Peptides/metabolism , Arthritis, Juvenile/immunology , Arthritis, Juvenile/physiopathology , Humans , Peptides/immunology
14.
J Infect Dis ; 184(10): 1328-30, 2001 Nov 15.
Article in English | MEDLINE | ID: mdl-11679924

ABSTRACT

Prednisolone slows the loss of CD4 T cells in individuals with human immunodeficiency virus (HIV) disease and inhibits antigen-induced apoptosis of recently HIV-infected CD4 cells in vitro. This study investigated whether dexamethasone inhibits the ability of macrophages to delete CD4 T cells via anti-CD4 antibody or immune-complexed HIV envelope protein gp120. Peripheral blood mononuclear cells from HIV-negative persons were incubated with CD4-reactive ch412 monoclonal antibody or with gp120/IgG immune complexes and resident macrophages, with and without dexamethasone. Dexamethasone inhibited CD4 cell deletion in a dose-dependent manner. The deletion of normal CD4 cells by macrophages from HIV-infected patients also was inhibited by dexamethasone. Furthermore, up-regulation of CD95 expression on T cells exposed to anti-CD4 and gp120/IgG, which predisposes T cells to CD95-mediated apoptosis, is inhibited by dexamethasone in a dose-dependent fashion. Dexamethasone inhibits the macrophage-mediated deletion of CD4 lymphocytes in HIV-infected persons.


Subject(s)
CD4-Positive T-Lymphocytes/drug effects , Dexamethasone/pharmacology , Glucocorticoids/pharmacology , HIV Infections/immunology , HIV-1 , Macrophages/drug effects , Adult , Antibodies, Monoclonal/pharmacology , Antibody-Dependent Cell Cytotoxicity/drug effects , CD4-Positive T-Lymphocytes/immunology , Dose-Response Relationship, Immunologic , HIV Envelope Protein gp120/immunology , Humans , Macrophages/immunology , Up-Regulation/drug effects , fas Receptor/immunology
17.
J Pharmacol Exp Ther ; 288(2): 613-9, 1999 Feb.
Article in English | MEDLINE | ID: mdl-9918566

ABSTRACT

Antiproliferative action of different pentacyclic triterpenes has repeatedly been reported, and some lipoxygenase inhibitors have been shown to induce cell death in various cell systems. Acetyl-11-keto-beta-boswellic acid (AKBA) is a pentacyclic triterpene that inhibits 5-lipoxygenase in a selective, enzymedirected, nonredox, and noncompetitive manner. To investigate a possible effect of AKBA on leukemic cell growth, proliferation of HL-60 and CCRF-CEM cells was assayed in the presence of AKBA and a structural analog without effect on 5-lipoxygenase, amyrin. Cell counts and [3H]thymidine incorporation were significantly reduced in a dose-dependent manner in the presence of AKBA (IC50 = 30 microM) but not amyrin. An additive effect of AKBA with the crosslinking of the CD95 receptor was also observed. Flow cytometric analysis of propidium iodide-stained cells indicated that the cells underwent apoptosis. This was confirmed by flow cytometric detection of sub-G1 peaks in AKBA-treated cells and by DNA laddering. However, because HL-60 and CCRF-CEM do not express 5-lipoxygenase mRNA constitutively, a mechanism distinct from inhibition of 5-lipoxygenase must account for the effect of AKBA. In a DNA relaxation assay with phiX174RF DNA, AKBA inhibited topoisomerase I from calf thymus at concentrations of >/=10 microM. A semiquantitative cDNA polymerase chain reaction approach was used to estimate the relative level of expression of topoisomerases in both cell lines. The data suggest that induction of apoptosis in HL-60 and CCRF-CEM by AKBA may be due to inhibition of topoisomerase I in these cells.


Subject(s)
Antineoplastic Agents/pharmacology , Apoptosis/drug effects , DNA Topoisomerases, Type II , Lipoxygenase Inhibitors/pharmacology , Topoisomerase I Inhibitors , Triterpenes/pharmacology , Animals , Antigens, Neoplasm , Arachidonate 5-Lipoxygenase/metabolism , Cell Division/drug effects , DNA Topoisomerases, Type I/biosynthesis , DNA Topoisomerases, Type I/metabolism , DNA Topoisomerases, Type II/biosynthesis , DNA, Neoplasm/drug effects , DNA, Neoplasm/metabolism , DNA-Binding Proteins , HL-60 Cells/drug effects , HL-60 Cells/enzymology , HL-60 Cells/pathology , Humans , Isoenzymes/biosynthesis , Leukemia, T-Cell/drug therapy , Leukemia, T-Cell/enzymology , Leukemia, T-Cell/pathology , Oleanolic Acid/analogs & derivatives , RNA, Messenger/metabolism , Rats , Tumor Cells, Cultured
18.
Pathobiology ; 67(5-6): 298-301, 1999.
Article in English | MEDLINE | ID: mdl-10725807

ABSTRACT

Macrophages (MPhi) affect the T cell response in two mutually exclusive ways: activation or deletion. A MPhi type with T cell activating functions (M1) is able to express and upregulate receptors of the B7 family. IFN-gamma favours this MPhi differentiation pathway via upregulation of CD80 (B7-1) and CD86 (B7-2). The treatment of MPhi with IFN-gamma enhances the alphaCD3-mediated T cell blast transformation and reduces the fraction of deleted T cells. This MPhi type may prevent antibody-mediated T cell destruction by the expression of costimulatory receptors. An IL-10-induced MPhi type (M2) fails to express costimulatory molecules of the B7 family but is an effective cell for T cell destruction. Forming cellular conjugates with T cells through antibodies or immune complexes, M2-MPhi preferentially delete targeted cells in vitro and in vivo.


Subject(s)
Antigen Presentation/immunology , Cytotoxicity, Immunologic/immunology , Lymphocyte Activation/immunology , Macrophages/immunology , T-Lymphocytes/immunology , Antibodies, Monoclonal/pharmacology , CD3 Complex/immunology , Cell Survival , Cells, Cultured , Cytotoxicity, Immunologic/drug effects , Flow Cytometry , Humans , Interferon-gamma/pharmacology , Lymphocyte Activation/drug effects , Macrophages/cytology , Macrophages/drug effects , Mitogens , Neutralization Tests , T-Lymphocytes/cytology , T-Lymphocytes/drug effects , T-Lymphocytes, Cytotoxic , Up-Regulation
19.
Immunology ; 95(3): 437-42, 1998 Nov.
Article in English | MEDLINE | ID: mdl-9824508

ABSTRACT

Macrophages are capable of destroying T cells with which they form cellular conjugates. The deletion can be prevented by the simultaneous transmission of costimulatory signals. We show here that T cells with elevated major histocompatibility complex (MHC) class I expression are resistant against macrophage-mediated cytotoxicity. T cells that express the CD45RO isotype, considered memory T cells, exhibit MHC class I antigen at higher density than naive CD45RA T cells and upregulate MHC class I expression promptly when they form cellular conjugates with macrophages. We confirm previous observations that CD45RA T cells are more susceptible to antibody- and macrophage-mediated deletion than memory CD45RO T cells. When MHC class I molecules are masked by specific monoclonal antibody or antibody Fab fragments, CD45RA T cells and CD45RO T cells exhibit equal susceptibility to macrophage cytotoxicity, demonstrating that the difference between CD45RA and CD45RO T cells in their sensitivity to macrophage cytotoxicity is determined by their MHC I expression. Separation of CD4 T cells from CD8 T cells deprives memory CD4 T cells of their resistance against macrophage cytotoxicity, suggesting that memory T cells' resistance against destruction by macrophages is controlled by regulatory T cells.


Subject(s)
Antibody-Dependent Cell Cytotoxicity , Histocompatibility Antigens Class I/metabolism , Immune Tolerance , Macrophages/immunology , T-Lymphocyte Subsets/immunology , Antibodies, Monoclonal/immunology , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Cell Communication/immunology , Cell Culture Techniques , Flow Cytometry , Humans , Leukocyte Common Antigens/analysis
20.
Immunology ; 94(3): 331-9, 1998 Jul.
Article in English | MEDLINE | ID: mdl-9767414

ABSTRACT

Naive T cells mount a vigorous proliferative response to superantigen (SAg) stimulation in vivo. The proliferative response is followed by a partial deletion of responder T cells. Part of the deletion process has recently been attributed to the action of regulatory cytotoxic T cells that recognize major histocompatibility complex (MHC) class I-associated antigen receptor determinants on the target cell surface. Responder T cells that survived the SAg response were found to be incapable of generating a secondary proliferative response to a SAg challenge. We show here that this 'anergy' is enforced by CD8-positive regulatory suppressive T cells. These regulatory cells inhibit cell division of preactivated T cells but not the Sag response of naive T cells. Regulatory T cells are not generated in the presence of cyclosporin A and, once activated, become inactivated or deleted when restimulated in the presence of this immunosuppressive drug.


Subject(s)
Clonal Anergy , Enterotoxins/pharmacology , Staphylococcus aureus/immunology , Superantigens/pharmacology , T-Lymphocytes/immunology , Animals , Cells, Cultured , Cyclosporine/pharmacology , Female , Flow Cytometry , Immunosuppressive Agents/pharmacology , Lymphocyte Activation , Mice , Mice, Inbred BALB C , T-Lymphocytes/drug effects
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