title: Defects of T-cell effector function and post-thymic maturation in X-linked hyper-IgM syndrome.
abstract: X-linked hyper-IgM syndrome (XHIM) results from mutations in the gene encoding for CD40 ligand (CD154). Patients with the syndrome suffer from infections with opportunistic pathogens such as Cryptosporidium and Pneumocystis carinii. In this study, we demonstrate that activated T cells from patients with XHIM produce markedly reduced levels of IFN-gamma, fail to induce antigen-presenting cells to synthesize IL-12, and induce greatly reduced levels of TNF-alpha. In addition, we show that the patients' circulating T lymphocytes of both the CD4(+) and CD8(+) subsets contain a markedly reduced antigen-primed population, as determined by CD45RO expression. Finally, we demonstrate that the defects in antigen priming are likely due to the lack of CD154 expression and insufficient costimulation of T cells by CD80/CD86 interactions. Taken together, this study offers a basis for the increased susceptibility of patients with XHIM to certain opportunistic infections.
authors: Mucosal Immunity Section, Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases/National Institutes of Health, Bethesda, Maryland 20892, USA.
authors: A
authors: A
authors: Jain
authors: T P
authors: TP
authors: Atkinson
authors: P E
authors: PE
authors: Lipsky
authors: J E
authors: JE
authors: Slater
authors: D L
authors: DL
authors: Nelson
authors: W
authors: W
authors: Strober
mesh_terms: D000293:Adolescent; D000328:Adult; D000938:Antigen-Presenting Cells; D018106:CD28 Antigens / Q000276:immunology; D023201:CD40 Ligand; D002648:Child; D015793:HLA-B7 Antigen / Q000276:immunology; D006801:Humans; D006942:Hypergammaglobulinemia / Q000276:immunology*; D007075:Immunoglobulin M / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D017493:Leukocyte Common Antigens / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000235:genetics; D009154:Mutation; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology* / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014960:X Chromosome
chemical_list: D018106:CD28 Antigens; D015793:HLA-B7 Antigen; D007075:Immunoglobulin M; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D023201:CD40 Ligand; D018664:Interleukin-12; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens