Altered responses to homeostatic cytokines in patients with idiopathic CD4 lymphocytopenia.

Idiopathic CD4 lymphocytopenia (ICL) is a rare immune deficiency characterized by a protracted CD4(+) T cell loss of unknown etiology and by the occurrence of opportunistic infections similar to those seen in AIDS. We investigated whether a defect in responses to cytokines that control CD4(+) T cell...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Florence Bugault, Daniela Benati, Luc Mouthon, Ivan Landires, Pierre Rohrlich, Vincent Pestre, Jacques Thèze, Olivier Lortholary, Lisa A Chakrabarti
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c2fbc163ebc34626bd73ba34577884d0
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:c2fbc163ebc34626bd73ba34577884d0
record_format	dspace
spelling	oai:doaj.org-article:c2fbc163ebc34626bd73ba34577884d02021-11-18T07:59:23ZAltered responses to homeostatic cytokines in patients with idiopathic CD4 lymphocytopenia.1932-620310.1371/journal.pone.0055570https://doaj.org/article/c2fbc163ebc34626bd73ba34577884d02013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23383227/?tool=EBIhttps://doaj.org/toc/1932-6203Idiopathic CD4 lymphocytopenia (ICL) is a rare immune deficiency characterized by a protracted CD4(+) T cell loss of unknown etiology and by the occurrence of opportunistic infections similar to those seen in AIDS. We investigated whether a defect in responses to cytokines that control CD4(+) T cell homeostasis could play a role in ICL. Immunophenotype and signaling responses to interleukin-7 (IL-7), IL-2, and thymic stromal lymphopoietin (TSLP) were analyzed by flow cytometry in CD4(+) T cells from 15 ICL patients and 15 healthy blood donors. The induction of phospho-STAT5 after IL-7 stimulation was decreased in memory CD4(+) T cells of some ICL patients, which correlated with a decreased expression of the IL-7Rα receptor chain (R = 0.74, p<0.005) and with lower CD4(+) T cell counts (R = 0.69, p<0.005). IL-2 responses were also impaired, both in the Treg and conventional memory subsets. Decreased IL-2 responses correlated with decreased IL-7 responses (R = 0.75, p<0.005), pointing to combined defects that may significantly perturb CD4(+) T cell homeostasis in a subset of ICL patients. Unexpectedly, responses to the IL-7-related cytokine TSLP were increased in ICL patients, while they remained barely detectable in healthy controls. TSLP responses correlated inversely with IL-7 responses (R = -0.41; p<0.05), suggesting a cross-regulation between the two cytokine systems. In conclusion, IL-7 and IL-2 signaling are impaired in ICL, which may account for the loss of CD4(+) T cell homeostasis. Increased TSLP responses point to a compensatory homeostatic mechanism that may mitigate defects in γc cytokine responses.Florence BugaultDaniela BenatiLuc MouthonIvan LandiresPierre RohrlichVincent PestreJacques ThèzeOlivier LortholaryLisa A ChakrabartiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 1, p e55570 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Florence Bugault Daniela Benati Luc Mouthon Ivan Landires Pierre Rohrlich Vincent Pestre Jacques Thèze Olivier Lortholary Lisa A Chakrabarti Altered responses to homeostatic cytokines in patients with idiopathic CD4 lymphocytopenia.
description	Idiopathic CD4 lymphocytopenia (ICL) is a rare immune deficiency characterized by a protracted CD4(+) T cell loss of unknown etiology and by the occurrence of opportunistic infections similar to those seen in AIDS. We investigated whether a defect in responses to cytokines that control CD4(+) T cell homeostasis could play a role in ICL. Immunophenotype and signaling responses to interleukin-7 (IL-7), IL-2, and thymic stromal lymphopoietin (TSLP) were analyzed by flow cytometry in CD4(+) T cells from 15 ICL patients and 15 healthy blood donors. The induction of phospho-STAT5 after IL-7 stimulation was decreased in memory CD4(+) T cells of some ICL patients, which correlated with a decreased expression of the IL-7Rα receptor chain (R = 0.74, p<0.005) and with lower CD4(+) T cell counts (R = 0.69, p<0.005). IL-2 responses were also impaired, both in the Treg and conventional memory subsets. Decreased IL-2 responses correlated with decreased IL-7 responses (R = 0.75, p<0.005), pointing to combined defects that may significantly perturb CD4(+) T cell homeostasis in a subset of ICL patients. Unexpectedly, responses to the IL-7-related cytokine TSLP were increased in ICL patients, while they remained barely detectable in healthy controls. TSLP responses correlated inversely with IL-7 responses (R = -0.41; p<0.05), suggesting a cross-regulation between the two cytokine systems. In conclusion, IL-7 and IL-2 signaling are impaired in ICL, which may account for the loss of CD4(+) T cell homeostasis. Increased TSLP responses point to a compensatory homeostatic mechanism that may mitigate defects in γc cytokine responses.
format	article
author	Florence Bugault Daniela Benati Luc Mouthon Ivan Landires Pierre Rohrlich Vincent Pestre Jacques Thèze Olivier Lortholary Lisa A Chakrabarti
author_facet	Florence Bugault Daniela Benati Luc Mouthon Ivan Landires Pierre Rohrlich Vincent Pestre Jacques Thèze Olivier Lortholary Lisa A Chakrabarti
author_sort	Florence Bugault
title	Altered responses to homeostatic cytokines in patients with idiopathic CD4 lymphocytopenia.
title_short	Altered responses to homeostatic cytokines in patients with idiopathic CD4 lymphocytopenia.
title_full	Altered responses to homeostatic cytokines in patients with idiopathic CD4 lymphocytopenia.
title_fullStr	Altered responses to homeostatic cytokines in patients with idiopathic CD4 lymphocytopenia.
title_full_unstemmed	Altered responses to homeostatic cytokines in patients with idiopathic CD4 lymphocytopenia.
title_sort	altered responses to homeostatic cytokines in patients with idiopathic cd4 lymphocytopenia.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/c2fbc163ebc34626bd73ba34577884d0
work_keys_str_mv	AT florencebugault alteredresponsestohomeostaticcytokinesinpatientswithidiopathiccd4lymphocytopenia AT danielabenati alteredresponsestohomeostaticcytokinesinpatientswithidiopathiccd4lymphocytopenia AT lucmouthon alteredresponsestohomeostaticcytokinesinpatientswithidiopathiccd4lymphocytopenia AT ivanlandires alteredresponsestohomeostaticcytokinesinpatientswithidiopathiccd4lymphocytopenia AT pierrerohrlich alteredresponsestohomeostaticcytokinesinpatientswithidiopathiccd4lymphocytopenia AT vincentpestre alteredresponsestohomeostaticcytokinesinpatientswithidiopathiccd4lymphocytopenia AT jacquestheze alteredresponsestohomeostaticcytokinesinpatientswithidiopathiccd4lymphocytopenia AT olivierlortholary alteredresponsestohomeostaticcytokinesinpatientswithidiopathiccd4lymphocytopenia AT lisaachakrabarti alteredresponsestohomeostaticcytokinesinpatientswithidiopathiccd4lymphocytopenia
_version_	1718422693961793536

Altered responses to homeostatic cytokines in patients with idiopathic CD4 lymphocytopenia.

Ejemplares similares