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Transforming growth factor-beta1-induced CD4+CD25+ regulatory T cells in vitro reverse and prevent a murine lupus-like syndrome of chronic graft-versus-host disease.
Br J Dermatol. 2008 Jun; 158(6):1197-209.BJ

Abstract

BACKGROUND

The suppressive mechanism of CD4+CD25+ regulatory T cells (Tregs) is poorly understood. It is also not known how to obtain enough peripheral Tregs, and how to make them effective in ameliorating a murine lupus-like syndrome of chronic graft-versus-host disease (cGVHD).

OBJECTIVES

To confirm the contribution of transforming growth factor (TGF)-beta1 in the function of CD4+CD25+ Tregs in vitro, and to identify in vivo suppressive effects of different Tregs generated through TGF-beta1.

METHODS

Suppressive effects of freshly isolated CD4+CD25+ Tregs, TGF-beta1-expanded CD4+CD25+ Tregs (eTregs) and TGF-beta1-induced CD4+CD25+ Tregs (iTregs) in vitro were assessed. Reverse transcription-polymerase chain reaction was used to detect Foxp3. The respective roles that different Tregs might play in controlling murine lupus-like syndrome of cGVHD were analysed.

RESULTS

TGF-beta1 was necessary for expanding the existing CD4+CD25+ Tregs in vitro, as well as converting peripheral CD4+CD25- T cells to CD4+CD25+ Tregs through upregulating CD25 and Foxp3. These eTregs and iTregs had a suppressive effect similar to that of freshly isolated CD4+CD25+ Tregs. The inhibitory function of iTregs could be partially blocked by anti-TGF-beta1. Importantly, it was revealed for the first time that both eTregs and iTregs had an inhibitory effect on reversing the morbidity of mice that had already developed anti-dsDNA, and iTregs gave more suppression than eTregs. Besides, iTregs could prevent the onset and slow the progress of disease in a significantly dose-dependent manner.

CONCLUSIONS

Results indicate that TGF-beta1 signalling is required to maintain the suppression of CD4+CD25+ Tregs in vitro and in vivo. Together, this study suggests a possible therapeutic role for iTregs in the treatment of murine lupus-like syndrome of cGVHD.

Authors+Show Affiliations

Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 69 Meishan Road, Hefei, Anhui 230032, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18410422

Citation

Su, H, et al. "Transforming Growth Factor-beta1-induced CD4+CD25+ Regulatory T Cells in Vitro Reverse and Prevent a Murine Lupus-like Syndrome of Chronic Graft-versus-host Disease." The British Journal of Dermatology, vol. 158, no. 6, 2008, pp. 1197-209.
Su H, Ye DQ, Wang BL, et al. Transforming growth factor-beta1-induced CD4+CD25+ regulatory T cells in vitro reverse and prevent a murine lupus-like syndrome of chronic graft-versus-host disease. Br J Dermatol. 2008;158(6):1197-209.
Su, H., Ye, D. Q., Wang, B. L., Fang, X. H., Chen, J., Wang, Q., Li, W. X., & Zhang, N. (2008). Transforming growth factor-beta1-induced CD4+CD25+ regulatory T cells in vitro reverse and prevent a murine lupus-like syndrome of chronic graft-versus-host disease. The British Journal of Dermatology, 158(6), 1197-209. https://doi.org/10.1111/j.1365-2133.2008.08555.x
Su H, et al. Transforming Growth Factor-beta1-induced CD4+CD25+ Regulatory T Cells in Vitro Reverse and Prevent a Murine Lupus-like Syndrome of Chronic Graft-versus-host Disease. Br J Dermatol. 2008;158(6):1197-209. PubMed PMID: 18410422.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Transforming growth factor-beta1-induced CD4+CD25+ regulatory T cells in vitro reverse and prevent a murine lupus-like syndrome of chronic graft-versus-host disease. AU - Su,H, AU - Ye,D-Q, AU - Wang,B-L, AU - Fang,X-H, AU - Chen,J, AU - Wang,Q, AU - Li,W-X, AU - Zhang,N, Y1 - 2008/04/10/ PY - 2008/4/16/pubmed PY - 2008/8/21/medline PY - 2008/4/16/entrez SP - 1197 EP - 209 JF - The British journal of dermatology JO - Br. J. Dermatol. VL - 158 IS - 6 N2 - BACKGROUND: The suppressive mechanism of CD4+CD25+ regulatory T cells (Tregs) is poorly understood. It is also not known how to obtain enough peripheral Tregs, and how to make them effective in ameliorating a murine lupus-like syndrome of chronic graft-versus-host disease (cGVHD). OBJECTIVES: To confirm the contribution of transforming growth factor (TGF)-beta1 in the function of CD4+CD25+ Tregs in vitro, and to identify in vivo suppressive effects of different Tregs generated through TGF-beta1. METHODS: Suppressive effects of freshly isolated CD4+CD25+ Tregs, TGF-beta1-expanded CD4+CD25+ Tregs (eTregs) and TGF-beta1-induced CD4+CD25+ Tregs (iTregs) in vitro were assessed. Reverse transcription-polymerase chain reaction was used to detect Foxp3. The respective roles that different Tregs might play in controlling murine lupus-like syndrome of cGVHD were analysed. RESULTS: TGF-beta1 was necessary for expanding the existing CD4+CD25+ Tregs in vitro, as well as converting peripheral CD4+CD25- T cells to CD4+CD25+ Tregs through upregulating CD25 and Foxp3. These eTregs and iTregs had a suppressive effect similar to that of freshly isolated CD4+CD25+ Tregs. The inhibitory function of iTregs could be partially blocked by anti-TGF-beta1. Importantly, it was revealed for the first time that both eTregs and iTregs had an inhibitory effect on reversing the morbidity of mice that had already developed anti-dsDNA, and iTregs gave more suppression than eTregs. Besides, iTregs could prevent the onset and slow the progress of disease in a significantly dose-dependent manner. CONCLUSIONS: Results indicate that TGF-beta1 signalling is required to maintain the suppression of CD4+CD25+ Tregs in vitro and in vivo. Together, this study suggests a possible therapeutic role for iTregs in the treatment of murine lupus-like syndrome of cGVHD. SN - 1365-2133 UR - https://www.unboundmedicine.com/medline/citation/18410422/Transforming_growth_factor_beta1_induced_CD4+CD25+_regulatory_T_cells_in_vitro_reverse_and_prevent_a_murine_lupus_like_syndrome_of_chronic_graft_versus_host_disease_ L2 - https://doi.org/10.1111/j.1365-2133.2008.08555.x DB - PRIME DP - Unbound Medicine ER -