Defects of T-cell effector function and post-thymic maturation in X-linked hyper-IgM syndrome
Ashish Jain, … , David L. Nelson, Warren Strober
Ashish Jain, … , David L. Nelson, Warren Strober
Published April 15, 1999
Citation Information: J Clin Invest. 1999;103(8):1151-1158. https://doi.org/10.1172/JCI5891.
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Article

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-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.

Authors

Ashish Jain, T. Prescott Atkinson, Peter E. Lipsky, Jay E. Slater, David L. Nelson, Warren Strober

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Percentage of cells with exclusive expression of CD45RA or CD45RO in the...
Percentage of cells with exclusive expression of CD45RA or CD45RO in the CD4+ and CD8+ T-cell subsets of six patients with XHIM and from 40 controls. (a) Patients with XHIM have a marked reduction in the percentage of CD4+ T cells with expression of CD45RO (P < 0.0002) and an increase in the percentage of CD4+ T cells with expression of CD45RA (P < 0.0001). (b) Patients with XHIM also have a significant reduction in the percentage of CD8+ T cells with expression of CD45RO (P < 0.002) and an increase in CD8+ T cells expressing CD45RA (P < 0.0001).