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 Citations (Scopus)

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 - 2015

Fingerprint

Lymphopenia
Mucous Membrane
T-Lymphocytes
Enterocytes
Inflammation
Th17 Cells
Fatty Acid-Binding Proteins
Interleukin-17
Opportunistic Infections
Virus Diseases
Myeloid Cells
CD4 Lymphocyte Count
C-Reactive Protein
Interferons
Interleukin-6
Flow Cytometry
Acquired Immunodeficiency Syndrome
Neutrophils
Tumor Necrosis Factor-alpha
Biomarkers

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Medicine(all)
  • Infectious Diseases

Cite this

Kovacs, S. B., Sheikh, V., Thompson, W. L., Morcock, D. R., Perez-Diez, A., Yao, M. 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

T-cell depletion in the colonic mucosa of patients with idiopathic CD4+ lymphopenia. / Kovacs, Stephen B.; Sheikh, Virginia; Thompson, William L.; Morcock, David R.; Perez-Diez, Ainhoa; Yao, Michael D.; Rupert, Adam W.; Utay, Netanya S.; Roby, Gregg; Freeman, Alexandra F.; Estes, Jacob D.; Sereti, Irini.

In: Journal of Infectious Diseases, Vol. 212, No. 10, 2015, p. 1579-1587.

Research output: Contribution to journalArticle

Kovacs, SB, Sheikh, V, Thompson, WL, Morcock, DR, Perez-Diez, A, Yao, MD, Rupert, AW, Utay, NS, Roby, G, Freeman, AF, Estes, JD & Sereti, I 2015, 'T-cell depletion in the colonic mucosa of patients with idiopathic CD4+ lymphopenia', Journal of Infectious Diseases, vol. 212, no. 10, pp. 1579-1587. https://doi.org/10.1093/infdis/jiv282
Kovacs SB, Sheikh V, Thompson WL, Morcock DR, Perez-Diez A, Yao MD et al. T-cell depletion in the colonic mucosa of patients with idiopathic CD4+ lymphopenia. Journal of Infectious Diseases. 2015;212(10):1579-1587. https://doi.org/10.1093/infdis/jiv282
Kovacs, Stephen B. ; Sheikh, Virginia ; Thompson, William L. ; Morcock, David R. ; Perez-Diez, Ainhoa ; Yao, Michael D. ; Rupert, Adam W. ; Utay, Netanya S. ; Roby, Gregg ; Freeman, Alexandra F. ; Estes, Jacob D. ; Sereti, Irini. / T-cell depletion in the colonic mucosa of patients with idiopathic CD4+ lymphopenia. In: Journal of Infectious Diseases. 2015 ; Vol. 212, No. 10. pp. 1579-1587.
@article{1ac400dd1b6f40b38e346ccd07015988,
title = "T-cell depletion in the colonic mucosa of patients with idiopathic CD4+ lymphopenia",
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.",
keywords = "Biomarkers, HIV/AIDS, Idiopathic CD4 lymphopenia, Inflammation, Mucosal immunity",
author = "Kovacs, {Stephen B.} and Virginia Sheikh and Thompson, {William L.} and Morcock, {David R.} and Ainhoa Perez-Diez and Yao, {Michael D.} and Rupert, {Adam W.} and Utay, {Netanya S.} and Gregg Roby and Freeman, {Alexandra F.} and Estes, {Jacob D.} and Irini Sereti",
year = "2015",
doi = "10.1093/infdis/jiv282",
language = "English (US)",
volume = "212",
pages = "1579--1587",
journal = "Journal of Infectious Diseases",
issn = "0022-1899",
publisher = "Oxford University Press",
number = "10",

}

TY - JOUR

T1 - T-cell depletion in the colonic mucosa of patients with idiopathic CD4+ lymphopenia

AU - Kovacs, Stephen B.

AU - Sheikh, Virginia

AU - Thompson, William L.

AU - Morcock, David R.

AU - Perez-Diez, Ainhoa

AU - Yao, Michael D.

AU - Rupert, Adam W.

AU - Utay, Netanya S.

AU - Roby, Gregg

AU - Freeman, Alexandra F.

AU - Estes, Jacob D.

AU - Sereti, Irini

PY - 2015

Y1 - 2015

N2 - 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.

AB - 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.

KW - Biomarkers

KW - HIV/AIDS

KW - Idiopathic CD4 lymphopenia

KW - Inflammation

KW - Mucosal immunity

UR - http://www.scopus.com/inward/record.url?scp=84977987888&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84977987888&partnerID=8YFLogxK

U2 - 10.1093/infdis/jiv282

DO - 10.1093/infdis/jiv282

M3 - Article

C2 - 25995198

AN - SCOPUS:84977987888

VL - 212

SP - 1579

EP - 1587

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

SN - 0022-1899

IS - 10

ER -