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2.
Cell Immunol ; 213(1): 72-81, 2001 Oct 10.
Article in English | MEDLINE | ID: mdl-11747358

ABSTRACT

Activated T cells undergo changes during their transition to T cell blasts and, subsequently, via a phase of anergy, to apoptosis. For example, activated murine T cell blasts express the B-cell-specific CD45R isoform, B220, a marker also present on T cells in mice and humans with defective Fas-mediated apoptosis in vivo, suggesting a role for B220 up-regulation in the transition of activation to apoptosis. Human T cells, activated in vitro with superantigens and mitogens, also express B220 as they undergo blastogenesis and cell cycle progression. B220 expression peaks on T cells undergoing apoptosis. CD43-hexasaccharide glycoform expression and lectin binding profiles indicate that B220 expression is reflective of altered O-linked glycan biosynthesis found in specific T cell subsets transitioning through the phases of proliferation, anergy, and apoptosis. Potential implications of these alterations include changes in lymphocyte adhesion and trafficking and homeostasis through altered sensitivity to Fas-dependent and independent pathways of apoptosis.


Subject(s)
Apoptosis , Leukocyte Common Antigens/biosynthesis , Polysaccharides/biosynthesis , T-Lymphocytes/metabolism , Adult , Animals , Annexin A5 , Antibodies, Monoclonal/immunology , Antibody Specificity , Cell Membrane/metabolism , Cells, Cultured , Enterotoxins/pharmacology , Humans , Leukocytes, Mononuclear/cytology , Leukocytes, Mononuclear/drug effects , Leukocytes, Mononuclear/metabolism , Lymphocyte Activation , Mice , Mitogens/pharmacology , Phytohemagglutinins/pharmacology , Protein Isoforms/biosynthesis , Staining and Labeling/methods , T-Lymphocytes/cytology , T-Lymphocytes/drug effects , Up-Regulation/drug effects
3.
Gastroenterology ; 121(4): 958-64, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11606509

ABSTRACT

Leukocyte adhesion deficiency 1 (LAD-1) is characterized by absent or dysfunctional beta2 integrin (CD18), leading to defective chemotaxis, adherence, phagocytosis, and bacterial killing. Colitis, except for rare intestinal necrotizing events, is not a well-recognized feature of this immunodeficiency. A case of nonspecific colitis clinically resembling Crohn's disease in a patient with the severe form of LAD-1 (0.5% < CD18) has been previously reported. We describe an adult patient with the moderate form of LAD-1 and chronic colitis characterized by extensive inflammation and ulceration of the right colon and terminal ileum, leading to adhesions and strictures. The chronic colitis described in this article associated with the dysfunctional neutrophils of LAD-1 represents a distinct pathology from the commonly encountered forms of inflammatory bowel disease (IBD). The existence of active IBD in the presence of dysfunctional CD18/CD11(a-b) intercellular adhesion molecules (ICAM-1) interaction is relevant to the proposed targeting of ICAM-1 for the treatment of Crohn's disease.


Subject(s)
Colitis/pathology , Crohn Disease/diagnosis , Leukocyte-Adhesion Deficiency Syndrome/physiopathology , Lymphocytes/immunology , Neutrophils/physiology , Antigens, CD/blood , Cell Adhesion , Child , Colitis/complications , Colitis/surgery , Flow Cytometry , Humans , Leukocyte-Adhesion Deficiency Syndrome/complications , Male , Neutrophils/microbiology , Neutrophils/pathology , Phagocytosis , Reference Values , Staphylococcus aureus/physiology
4.
Clin Immunol ; 100(3): 270-6, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11513540

ABSTRACT

The convergence of innate and adaptive immunity is critical for host defense, allowing for early protection and the generation of specific responses. STAT-4 is at that point of convergence, unifying the IFNalpha and IL-12 pathways. Activation of STAT-4 is crucial to T cell polarization, B cell and NK cell activation, and the control of intracellular pathogens. However, techniques to detect phosphorylated STAT-4 are cumbersome and require many cells. We have developed a flow cytometric detection technique to investigate IL-12 signaling in human peripheral blood mononuclear cells. Using different polyclonal antibodies that recognize either total STAT-4 protein or tyrosine-phosphorylated STAT-4, we can easily detect IL-12 and IFNalpha signaling in PHA/IL-2 blasts derived from peripheral blood lymphocytes. This technique not only allows us to evaluate IL-12 signaling, but it is also less time consuming and labor intensive than alternative methods. Using this flow cytometry-based method, we should be able to detect patients with defects in IL-12 receptor signal transduction, who typically present with disseminated nontuberculous mycobacterial infections.


Subject(s)
DNA-Binding Proteins/analysis , Trans-Activators/analysis , Animals , DNA-Binding Proteins/metabolism , Dose-Response Relationship, Drug , Flow Cytometry , Interferon-alpha/pharmacology , Interleukin-12/pharmacology , Mice , Mice, Inbred BALB C , Phosphorylation , STAT4 Transcription Factor , Trans-Activators/metabolism
5.
Pediatr Clin North Am ; 47(6): 1275-89, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11130996

ABSTRACT

Mutations predisposing to infections with intracellular pathogens and affecting Th1 T-cells and monocytes have been identified in the past few years. In this article, the authors review the interaction of T cells and monocytes in the context of host defense against intracellular pathogens. Known genetic defects in these pathways are summarized.


Subject(s)
Immunologic Deficiency Syndromes/diagnosis , Immunologic Deficiency Syndromes/immunology , Monocytes, Activated Killer/immunology , T-Lymphocytes, Helper-Inducer/immunology , Child , Child, Preschool , Female , Humans , Immunity, Cellular , Immunologic Deficiency Syndromes/genetics , Infant , Infant, Newborn , Male
6.
Pediatrics ; 106(4): 835-7, 2000 Oct.
Article in English | MEDLINE | ID: mdl-11015530

ABSTRACT

Patients with phagocyte defects frequently develop bacterial or fungal pneumonias, but they are not considered to be at increased risk for viral infections. We describe 3 patients with known phagocyte immunodeficiencies who developed lower respiratory tract infections (LRTI) caused by respiratory syncytial virus (RSV). All 3 patients had dense pneumonias as indicated by computed tomography scan of the lungs and RSV was recovered. We conclude that RSV can present as a dense pneumonia in patients with phagocyte defects. Along with common pathogens causing LRTI, RSV should be considered in the differential diagnosis. Viral cultures as well as rapid antigen detection assays for respiratory viruses should be included in the evaluation of LRTI in patients with phagocyte defects. respiratory syncytial virus, phagocyte, immunodeficiency, pneumonia.


Subject(s)
Phagocyte Bactericidal Dysfunction/complications , Pneumonia, Viral/etiology , Receptors, Interferon/deficiency , Respiratory Syncytial Virus Infections/etiology , Respiratory Syncytial Virus, Human , Child , Child, Preschool , Granulomatous Disease, Chronic/complications , Granulomatous Disease, Chronic/diagnostic imaging , Humans , Interferon-gamma , Male , Pneumonia, Viral/diagnostic imaging , Respiratory Syncytial Virus Infections/diagnostic imaging , Tomography, X-Ray Computed , Interferon gamma Receptor
7.
J Pediatr ; 135(5): 640-3, 1999 Nov.
Article in English | MEDLINE | ID: mdl-10547254

ABSTRACT

Interferon-gamma receptor deficiency is a recently described immunodeficiency that is associated with onset of severe mycobacterial infections in childhood. We describe the occurrence of symptomatic and often severe viral infections in 4 patients with interferon-gamma receptor deficiency and mycobacterial disease. The viral pathogens included herpes viruses, parainfluenza virus type 3, and respiratory syncytial virus. We conclude that patients with interferon-gamma receptor deficiency and mycobacterial disease have increased susceptibility to some viral pathogens.


Subject(s)
Mycobacterium Infections/immunology , Receptors, Interferon/deficiency , Virus Diseases/immunology , Antigens, CD/genetics , Child , Child, Preschool , Female , Humans , Immunologic Deficiency Syndromes/genetics , Immunologic Deficiency Syndromes/immunology , Infant , Male , Phenotype , Receptors, Interferon/immunology , Interferon gamma Receptor
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