Phenotypic alterations of dendritic cells are involved in suppressive activity of trichosanthin-induced CD8+CD28- regulatory T cells.
The nature and differentiation of regulatory CD8(+)CD28(-) T cells are poorly understood. In this study, we demonstrate that native Ag trichosanthin (Tk), a highly purified linear peptide isolated from a Chinese medicinal herb, is able to induce strong suppression of OVA-specific lymphoproliferation at low concentrations via activation of IL-4/IL-10-secreting CD8(+)CD28(-) regulatory T cells (Tregs). To elucidate the underlying mechanisms, we firstly identified two types of mouse inbred strains, high susceptible (HS) and low susceptible, for the Tk-related suppression. They are H-2(d) (or H-2(b)) and H-2(k), respectively. The suppression is evoked only if bone marrow-derived dendritic cells (BDCs) instead of purified T cells are treated with Tk in an OVA-specific T-BDC interaction. Moreover, a special pattern of cytokine/transcription factors (IL-4(+)IL-10(+)IFN-gamma(-)Gata3(+)T-bet(-)) during suppressed OVA-specific T cell proliferation was observed in HS C57BL/6 but not in low-susceptible C3H/He mice. Consistently, the percentage of CD8(+)CD28(-) Tregs preferentially expanded from 5.5 to 26.1% in the presence of Tk, an occurrence that was also detected only in HS C57BL/6 mice. These expanded Tregs were able to induce a strong inhibition of one-way MLCs, which indicated that the Tk-induced hyporeaction and the activation of CD8(+)CD28(-) Tregs might be under the influence of different genetic backgrounds. Additionally, obvious alterations of phenotypic parameters of BDCs after Tk stimulation were also identified, including enhanced production of IL-10, decreased secretion of IL-12, and detection of Jagged1, a Notch ligand on BDCs. Collectively, our data suggest that the changed APC-related factors are essential, at least in part, for the activation and differentiation of Tk-induced CD8(+)CD28(-) Tregs.
Wang
Baolong
B
Shanghai Institute of Immunology, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Jiao
Zhijun
Z
Shao
Xiaoyi
X
Lu
Liming
L
Yang
Neng
N
Zhou
Xiaorong
X
Xin
Lijun
L
Zhou
Yun
Y
Chou
Kuang-Yen
KY
D000818:Animals; D018106:CD28 Antigens / Q000378:metabolism; D016827:CD8 Antigens / Q000096:biosynthesis*; D002460:Cell Line; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D015536:Down-Regulation / Q000276:immunology*; D020022:Genetic Predisposition to Disease; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008806:Mice, Inbred AKR; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D013045:Species Specificity; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D029778:Trichosanthes / Q000276:immunology*; D015978:Trichosanthin / Q000494:pharmacology*
D018106:CD28 Antigens; D016827:CD8 Antigens; D015978:Trichosanthin