T-cell depletion in the colonic mucosa of patients with idiopathic CD4+ lymphopenia

Stephen B. Kovacs, Virginia Sheikh, William L. Thompson, David R. Morcock, Ainhoa Perez-Diez, Michael D. Yao, Adam W. Rupert, Netanya S. Utay, Gregg Roby, Alexandra F. Freeman, Jacob D. Estes, Irini Sereti

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Idiopathic CD4+ lymphopenia (ICL) is a rare syndrome characterized by low peripheral CD4+ T-cell counts that can lead to serious opportunistic infections. The pathogenesis of ICL remains unclear, and whether effector sites are also lymphopenic is unknown. In this study, rectosigmoid mucosal biopsy specimens from patients with ICL and healthy controls were evaluated. Significant T-cell lymphopenia was observed in the mucosal tissue of patients with ICL by flow cytometry and immunohistochemistry, compared with healthy controls. Functional capacity of T cells, assessed by production of interferon γ and interleukin 17, was preserved in the mucosa of patients with ICL. In contrast to T lymphocytes, the frequency of myeloid cells (neutrophils and macrophages) was elevated in the colonic mucosa of patients with ICL. Despite the observed mucosal abnormalities, plasma levels of intestinal fatty acid binding protein, a marker of enterocyte turnover and other inflammatory biomarkers, including interleukin 6, C-reactive protein, and tumor necrosis factor, were not elevated in patients with ICL, compared with healthy controls, whereas soluble CD14 levels were minimally elevated. These data suggest that patients with ICL, despite gut mucosal lymphopenia and local tissue inflammation, have preserved enterocyte turnover and T-helper type 17 cells with minimal systemic inflammation. These observations highlight differences from patients with human immunodeficiency virus infection, with or without AIDS, and may partially explain their distinct clinical prognosis.

Original languageEnglish (US)
Pages (from-to)1579-1587
Number of pages9
JournalJournal of Infectious Diseases
Volume212
Issue number10
DOIs
StatePublished - Jan 1 2015

Keywords

  • Biomarkers
  • HIV/AIDS
  • Idiopathic CD4 lymphopenia
  • Inflammation
  • Mucosal immunity

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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    Kovacs, S. B., Sheikh, V., Thompson, W. L., Morcock, D. R., Perez-Diez, A., Yao, M. D., Rupert, A. W., Utay, N. S., Roby, G., Freeman, A. F., Estes, J. D., & Sereti, I. (2015). T-cell depletion in the colonic mucosa of patients with idiopathic CD4+ lymphopenia. Journal of Infectious Diseases, 212(10), 1579-1587. https://doi.org/10.1093/infdis/jiv282