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 Blood, 1 September 2008, Vol. 112, No. 5, pp. 2129-2138.
Prepublished online as a Blood First Edition Paper on June 12, 2008; DOI 10.1182/blood-2008-02-140277.

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TRANSPLANTATION

In vivo–activated CD103+CD4+ regulatory T cells ameliorate ongoing chronic graft-versus-host disease

Dongchang Zhao1,2, Chunyan Zhang1,2, Tangsheng Yi3, Chia-Lei Lin1,2, Ivan Todorov1, Fouad Kandeel1, Stephen Forman2, and Defu Zeng13

1 Department of Diabetes/Endocrinology, 2 Division of Hematology/Hematopoietic Cell Transplantation, and 3 City of Hope Graduate School of Biological Sciences, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA

CD103 ({alpha}Eβ7) has been shown to be an excellent marker for identifying in vivo–activated FoxP3+CD4+ regulatory T (Treg) cells. It is unknown whether reinfusion of in vivo–activated donor-type CD103+ Treg cells from recipient can ameliorate ongoing chronic graft-versus-host disease (GVHD). Here, we showed that, in a chronic GVHD model of DBA/2 (H-2d) donor to BALB/c (H-2d) recipient, donor-type CD103+ Treg cells from recipients were much more potent than CD25hi natural Treg cells from donors in reversing clinical signs of GVHD and tissue damage. Furthermore, in contrast to CD25hi natural Treg cells, CD103+ Treg cells expressed high levels of CCR5 but low levels of CD62L and directly migrated to GVHD target tissues. In addition, the CD103+ Treg cells strongly suppressed donor CD4+ T-cell proliferation; they also induced apoptosis of in vivo–activated CD4+ T and B cells and significantly reduced pathogenic T and B cells in GVHD target tissues. These results indicate that CD103+ Treg cells from chronic GVHD recipients are functional, and reinfusion of the CD103+ Treg cells can shift the balance between Treg cells and pathogenic T cells in chronic GVHD recipients and ameliorate ongoing disease.


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