Phenotypic differences of CD4(+) T cells in response to red blood cell immunization in transfused sickle cell disease patients

Eur J Immunol. 2015 Jun;45(6):1868-79. doi: 10.1002/eji.201445187. Epub 2015 Apr 15.


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.

Keywords: Alloimmunization; CD4+ T cells; Jkb; Sickle cell disease; Th17.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Anemia, Sickle Cell / immunology*
  • Anemia, Sickle Cell / metabolism*
  • Anemia, Sickle Cell / therapy
  • Autoimmunity
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism*
  • Case-Control Studies
  • Cell Differentiation / immunology
  • Cytokines / biosynthesis
  • Erythrocytes / immunology*
  • Female
  • Humans
  • Immunization
  • Immunologic Memory
  • Immunophenotyping
  • Lymphocyte Activation / immunology
  • Male
  • Middle Aged
  • Phenotype
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism*
  • Toll-Like Receptors / metabolism
  • Transfusion Reaction
  • Young Adult


  • Cytokines
  • Toll-Like Receptors