Idiopathic CD4+ T-cell lymphocytopenia is associated with impaired membrane expression of the chemokine receptor CXCR4

Blood. 2010 May 6;115(18):3708-17. doi: 10.1182/blood-2009-02-202796. Epub 2009 Dec 28.

Abstract

Idiopathic CD4(+) T-cell lymphocytopenia (ICL) is a rare acquired T-cell immunodeficiency of unknown pathogenic basis. Six adults with ICL who developed opportunistic infections were investigated using extensive immunophenotyping analysis and functional evaluation of the chemokine receptor CXCR4. For all 6 patients studied, a profound defect in CXCR4 expression was detected at the surface of CD4(+) T lymphocytes, in association with an abnormal intracellular accumulation of CXCR4 and of its natural ligand, the chemokine CXCL12. For all patients studied, CD4(+) T-cell chemotactic response toward CXCL12 was decreased, whereas sensitivity to CXCL8 was preserved. CXCR4 recovery after ligand-induced endocytosis was impaired in ICL CD4(+) T cells. Upon in vitro addition of interleukin-2 (IL-2), membrane expression of CXCR4 returned to normal levels in 5 of 6 patients, whereas intracellular accumulation of CXCR4 and CXCL12 disappeared. Upon therapeutic administration of IL-2, CD4(+) T-cell count and membrane CXCR4 expression and function improved over time in 3 of 4 patients treated. Therefore, our data indicate that ICL is associated with defective surface expression of CXCR4, which may be reversed by IL-2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • CD4-Positive T-Lymphocytes / metabolism*
  • Cell Membrane / metabolism*
  • Cells, Cultured
  • Chemokines
  • Chemotaxis
  • Flow Cytometry
  • Humans
  • Immunophenotyping
  • Interleukin-2 / therapeutic use
  • Middle Aged
  • Opportunistic Infections / metabolism*
  • Receptors, CXCR4 / metabolism*
  • T-Lymphocytopenia, Idiopathic CD4-Positive / metabolism*
  • T-Lymphocytopenia, Idiopathic CD4-Positive / therapy
  • Young Adult

Substances

  • Chemokines
  • Interleukin-2
  • Receptors, CXCR4