title: Immunologic characterization suggests reduced alloimmunization in a murine model of thalassemia intermedia.
abstract: BACKGROUND
  Transfusion therapy remains a mainstay of treatment for patients with thalassemia major and to a lesser extent for the less anemic patients with thalassemia intermedia. We have previously reported a role for regulatory T cells (Tregs) in the control of antibody responses in wild-type C57BL/6 (WT) mice exposed to allogeneic red blood cell transfusions. As an initial step to study and characterize immune regulation in thalassemias, we performed an immunologic cell-type characterization of C57BL/6 Hbb(th-1)/Hbb(th-1) mouse model of thalassemia intermedia (Thal) in steady state as well as after transfusions with allogeneic blood.
  
  
  METHODS
  The myeloid and lymphocyte compartments including Tregs and T helper (Th) responses were analyzed in transfusion naive Thal and WT mouse spleens. The effect of allogeneic transfusions on Treg and global T helper responses was also measured.
  
  
  RESULTS
  We found elevated levels and activity of splenic Tregs in Thal mice with lower Th type 1/Th type 2 ratios before as well as after transfusion. Furthermore, pretransfused Thal mice had altered ratios of the splenic myeloid compartment with increased proportion of macrophages but lower frequency of conventional dendritic cells. Surprisingly, transfusions resulted in lower alloimmunization levels in Thal compared to WT mice.
  
  
  CONCLUSIONS
  These data suggest that this experimental model of thalassemia intermedia has an intrinsic alteration in splenic immunoregulation with an increased resistance to alloimmunization, raising the possibility that studying this animal model may help to identify potential immunoregulatory networks to inhibit alloimmunization.
authors.affiliation: Laboratory of Complement Biology, New York Blood Center, New York, New York.
authors.forename: Weili
authors.initials: W
authors.lastname: Bao
authors.forename: Hui
authors.initials: H
authors.lastname: Zhong
authors.forename: Karina
authors.initials: K
authors.lastname: Yazdanbakhsh
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D017707:Erythrocyte Transfusion / Q000009:adverse effects*; D006801:Humans; D051379:Mice; D013154:Spleen / Q000276:immunology / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology* / Q000473:pathology; D017086:beta-Thalassemia / Q000276:immunology* / Q000473:pathology / Q000628:therapy*