Defects of T-cell effector function and post-thymic maturation in X-linked hyper-IgM syndrome
AUTOR(ES)
Jain, Ashish
FONTE
American Society for Clinical Investigation
RESUMO
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-γ, fail to induce antigen-presenting cells to synthesize IL-12, and induce greatly reduced levels of TNF-α. 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.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=408278Documentos Relacionados
- X inactivation and immunocompetence in female carriers of the X-linked hyper-IgM syndrome.
- Absence of IgD-CD27(+) memory B cell population in X-linked hyper-IgM syndrome.
- Somatic mutation of human immunoglobulin V genes in the X-linked HyperIgM syndrome.
- Organization of the human CD40L gene: implications for molecular defects in X chromosome-linked hyper-IgM syndrome and prenatal diagnosis.
- Signaling through CD40 rescues IgE but not IgG or IgA secretion in X-linked immunodeficiency with hyper-IgM.