Response
We observed that the percentage of CD103+ cells among CD4+FoxP3+ regulatory T (Treg) cells of donor DBA/2 mice was less than 10% before transplantation, and the percentage of CD103+ cells among donor-type CD4+Foxp3+ Treg cells increased to more than 55% in BALB/c recipients with chronic graft-versus-host disease (GVHD) and 70% in recipients without chronic GVHD after hematopoietic cell transplantation (HCT).1 We also observed that the percentage of CD103+ cells among Foxp3+CD4+ Treg cells in donor C57BL/6 mice was approximately 20% (mean ± SE: 20.7 ± 1.7%, N = 4) before HCT, and the percentage of CD103+ Treg cells increased to around 40% (mean ± SE: 44.3 ± 2.0%, N = 4) in BALB/c recipients with acute GVHD. These results indicate that inflammation, especially chronic inflammation, can augment the expression of CD103 on mouse Foxp3+ Treg cells, although the percentage of CD103+ cells among Foxp3+ Treg cells can differ up to certain levels in different mouse strains or different housing environments, because the percentage of CD103+ Treg cells in our DBA/2 mice is around 10%, but the percentage of our C57BL/6 mice is around 20%; the percentage of CD103+ Treg cells in our C57BL/6 mice is approximately 20%, but the percentage in C57BL/6 mice in Hühn's reports is approximately 30%.2
It has been well documented that the percentage of CD103+ cells among Foxp3+CD4+ Treg cells in healthy humans is low, around 5%.3,–5 However, it is still unknown whether Fopx3+ Treg cells in human HCT recipients express CD103. It has been shown that the percentage of CD103+ cells among CD25hiCD4+ T cells was significantly higher than that among CD25−CD4+ T cells in patients with multiple sclerosis.6 In addition, in vitro TGF-β–induced Treg cells were all CD103+.7 TGF-β secretion is usually up-regulated in patients with chronic inflammation.8 Therefore, although most of the Foxp3+ Treg cells in normal humans do not express CD103, we cannot exclude the possibility that Foxp3+ Treg cells in patients with chronic inflammation (such as chronic GVHD) will up-regulate CD103 expression. Because it has been reported that effector/memory Foxp3+ Treg cells express CCR6 in mice9 and they express CD39 in multiple sclerosis patients,10 comparison of expression of CD103, CCR6, and CD39 by Foxp3+ Treg cells in patients with chronic inflammation is required to find out which one is best for identifying the Foxp3 Treg cells.
Authorship
Acknowledgments: We thank Dr Jochen Hühn at Experimentelle Rheumatologie, Charite Universitaestsmedizin Berlin for his in-depth discussion, and Dr M. Kleinewiefeld and colleagues for their comments on differential surface expression of CD103 by murine and human Foxp3+ Treg cells.
This work was supported by a grant from the National Institutes of Health (Bethesda, MD; R01 AI066008 to D. Zeng). Approval for this study was obtained from the City of Hope National Medical Center Institutional Review Board.
Conflict-of-interest disclosure: The authors declare no competing financial interests.
Correspondence: Defu Zeng, Department of Hematology and Hematopoietic Cell Transplantation, Beckman Research Institute, City of Hope National Medical Center, 1500 East Duarte Road, Duarte, CA 91010; e-mail: dzeng@coh.org.
References
National Institutes of Health
