title: Idiopathic CD4+ T-cell lymphocytopenia is associated with impaired membrane expression of the chemokine receptor CXCR4.
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.
authors.affiliation: Institut Pasteur, Unité de Régulation des Infections Rétrovirales, Paris, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Scott-Algara
authors.forename: Karl
authors.initials: K
authors.lastname: Balabanian
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Chakrabarti
authors.forename: Luc
authors.initials: L
authors.lastname: Mouthon
authors.forename: Françoise
authors.initials: F
authors.lastname: Dromer
authors.forename: Céline
authors.initials: C
authors.lastname: Didier
authors.forename: Fernando
authors.initials: F
authors.lastname: Arenzana-Seisdedos
authors.forename: Olivier
authors.initials: O
authors.lastname: Lortholary
mesh_terms: D000293:Adolescent; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D018925:Chemokines; D002633:Chemotaxis; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D007376:Interleukin-2 / Q000627:therapeutic use; D008875:Middle Aged; D009894:Opportunistic Infections / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000378:metabolism*; D018344:T-Lymphocytopenia, Idiopathic CD4-Positive / Q000378:metabolism* / Q000628:therapy; D055815:Young Adult
chemical_list: D018925:Chemokines; D007376:Interleukin-2; D019718:Receptors, CXCR4