WB and HZ contributed equally to this manuscript.
Immunologic characterization suggests reduced alloimmunization in a murine model of thalassemia intermedia
Article first published online: 5 MAY 2014
© 2014 AABB
Volume 54, Issue 11, pages 2880–2891, November 2014
How to Cite
Bao, W., Zhong, H. and Yazdanbakhsh, K. (2014), Immunologic characterization suggests reduced alloimmunization in a murine model of thalassemia intermedia. Transfusion, 54: 2880–2891. doi: 10.1111/trf.12683
This work was supported in part by National Heart, Lung, and Blood Institute Grant R21HL097350 (KY).
- Issue published online: 10 NOV 2014
- Article first published online: 5 MAY 2014
- Manuscript Accepted: 2 MAR 2014
- Manuscript Revised: 24 FEB 2014
- Manuscript Received: 8 JAN 2014
- National Heart, Lung, and Blood Institute. Grant Number: R21HL097350
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 Hbbth-1/Hbbth-1 mouse model of thalassemia intermedia (Thal) in steady state as well as after transfusions with allogeneic blood.
Study Design and 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.
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.
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.