Absence of CD40-CD40 ligand interactions in X-linked hyper-IgM syndrome does not affect differentiation of T helper cell subsets.
The aim of this study was to investigate the effect of absent CD40-CD40 ligand interactions in patients with X-linked hyper-IgM syndrome (XHIGM) on the generation of Th1 and Th2 immunity. Whole blood from patients and sex- and age-matched controls was stimulated with phorbol myristate acetate (PMA) and calcium ionophore A23187 in the presence of Brefeldin A. After 5 h, cellular production of interferon-gamma, IL-4, tumour necrosis factor-alpha and IL-2 was measured by intracellular cytokine staining and flow cytometry. This method has been shown previously to preferentially activate memory T cells and in preliminary experiments cells making these cytokines were found to be predominantly CD45RO+. No differences in the proportion of T cells (CD3+) or T cell subsets (CD4+/CD8+) secreting these cytokines between XHIGM patients and age- and sex-matched controls were observed. In addition, production of IL-12 and IL-6 by monocytes in response to lipopolysaccharide and CD40 stimulation was equivalent in patients and controls. These results suggest that development of Th1 or Th2 memory cells in patients with XHIGM is unaffected by the absence of functional CD40 ligand. Rather, the susceptibility of these patients to intracellular pathogens, such as Pneumocystis carinii and Cryptosporidium parvum, is more likely to be due to an inability to activate the effector arm of the cellular immune response.
Uronen
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Immunobiology Unit, Institute of Child Health, University College London, London, UK.
Callard
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D000293:Adolescent; D000328:Adult; D017252:CD3 Complex / Q000032:analysis; D019013:CD40 Antigens / Q000502:physiology*; D023201:CD40 Ligand; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D002454:Cell Differentiation; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D006942:Hypergammaglobulinemia / Q000235:genetics / Q000276:immunology*; D007075:Immunoglobulin M / Q000276:immunology*; D007156:Immunologic Memory; D007223:Infant; D007476:Ionophores / Q000494:pharmacology; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008222:Lymphokines / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D015846:Monokines / Q000378:metabolism; D013577:Syndrome; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D014960:X Chromosome / Q000235:genetics*
D017252:CD3 Complex; D019013:CD40 Antigens; D007075:Immunoglobulin M; D007476:Ionophores; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D008222:Lymphokines; D008562:Membrane Glycoproteins; D015846:Monokines; D023201:CD40 Ligand; D000001:Calcimycin; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium