title: Phenotypic differences of CD4(+) T cells in response to red blood cell immunization in transfused sickle cell disease patients.
abstract: Alloimmunization against red blood cells (RBCs) is the main immunological risk associated with transfusion in patients with sickle cell disease (SCD). However, about 50-70% of SCD patients never get immunized despite frequent transfusion. In murine models, CD4(+) T cells play a key role in RBC alloimmunization. We therefore explored and compared the CD4(+) T-cell phenotypes and functions between a group of SCD patients (n = 11) who never became immunized despite a high transfusion regimen and a group of SCD patients (n = 10) who had become immunized (at least against Kidd antigen b) after a low transfusion regimen. We studied markers of CD4(+) T-cell function, including TLR, that directly control lymphocyte function, and their spontaneous cytokine production. We also tested responders for the cytokine profile in response to Kidd antigen b peptides. Low TLR2/TLR3 expression and, unexpectedly, strong expression of CD40 on CD4(+) T cells were associated with the nonresponder status, whereas spontaneous expression of IL-10 by CD4(+) T cells and weak Tbet expression were associated with the responder status. A Th17 profile was predominant in responders when stimulated by Jb(k) . These findings implicate CD4(+) T cells in alloimmunization in humans and suggest that they may be exploited to differentiate responders from nonresponders.
authors.affiliation: Etablissement Français du Sang, Créteil, France.|Inserm, U955, Equipe 2, Créteil, France.
authors.forename: Benoît
authors.initials: B
authors.lastname: Vingert
authors.affiliation: Etablissement Français du Sang, Créteil, France.|Inserm, U955, Equipe 2, Créteil, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Tamagne
authors.affiliation: Inserm, U955, Equipe 2, Créteil, France.|AP-HP, Hôpital H. Mondor-A, Chenevier, Service Maladies Génétiques du Globule Rouge, Créteil, France.
authors.forename: Anoosha
authors.initials: A
authors.lastname: Habibi
authors.affiliation: Etablissement Français du Sang, Créteil, France.|Inserm, U955, Equipe 2, Créteil, France.
authors.forename: Sadaf
authors.initials: S
authors.lastname: Pakdaman
authors.affiliation: Etablissement Français du Sang, Créteil, France.|Inserm, U955, Equipe 2, Créteil, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Ripa
authors.affiliation: Etablissement Français du Sang, Créteil, France.|Inserm, U955, Equipe 2, Créteil, France.
authors.forename: Rahma
authors.initials: R
authors.lastname: Elayeb
authors.affiliation: Inserm, U955, Equipe 2, Créteil, France.|AP-HP, Hôpital H. Mondor-A, Chenevier, Service Maladies Génétiques du Globule Rouge, Créteil, France.|Faculté de médecine, Université Paris Est, Créteil, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Galacteros
authors.affiliation: Etablissement Français du Sang, Créteil, France.|Inserm, U955, Equipe 2, Créteil, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Bierling
authors.affiliation: Etablissement Français du Sang, Créteil, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Ansart-Pirenne
authors.affiliation: Inserm, U955, Equipe 2, Créteil, France.|AP-HP, Hôpital H. Mondor-A, Chenevier, Service Maladies Génétiques du Globule Rouge, Créteil, France.|Faculté de médecine, Université Paris Est, Créteil, France.
authors.forename: Pablo
authors.initials: P
authors.lastname: Bartolucci
authors.affiliation: Etablissement Français du Sang, Créteil, France.|Inserm, U955, Equipe 2, Créteil, France.|Faculté de médecine, Université Paris Est, Créteil, France.
authors.forename: France
authors.initials: F
authors.lastname: Noizat-Pirenne
mesh_terms: D000293:Adolescent; D000328:Adult; D000755:Anemia, Sickle Cell / Q000276:immunology* / Q000378:metabolism* / Q000628:therapy; D015551:Autoimmunity; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D016022:Case-Control Studies; D002454:Cell Differentiation / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D004912:Erythrocytes / Q000276:immunology*; D005260:Female; D006801:Humans; D007114:Immunization; D007156:Immunologic Memory; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D051193:Toll-Like Receptors / Q000378:metabolism; D065227:Transfusion Reaction; D055815:Young Adult
chemical_list: D016207:Cytokines; D051193:Toll-Like Receptors
keywords: Alloimmunization; CD4+ T cells; Jkb; Sickle cell disease; Th17