LF 15-0195 generates synergistic tolerance by promoting formation of CD4+CD25+CTLA4+ T cells.
The purpose of the present study was to investigate the influence of 15-deoxyspergualin (LF) on the phenotypes and functions of dendritic cells (DCs) and T cells and to further illustrate the mechanism of LF-inducing immunologic tolerance. DCs from mice were cultured and treated with varying doses of LF at specific time-points. Fluorescence-activated cell sorting (FACS) was used to verify the changes of phenotypes in the cultured DCs labeled with fluorescent antibody. DCs were also used as stimulators in mixed leukocyte reaction to detect their ability to stimulate T-cell proliferation. DCs and T cells, treated with or without LF, were cultured together; phenotypes and cytokine profile of the T cells were identified and assayed by FACS and enzyme-linked immunosorbent assay. LF induced a dose- and time-dependent suppression of maturation of DCs and a dose-dependent suppression of T-cell proliferation in mixed leukocyte reaction when LF-treated DCs were used as stimulators. LF-treated DCs, cultured with naive T cells, could promote the formation of CD4+CD25+CTLA4+ T-cell subtypes and the production of higher levels of interleukin-10. It was suggested that the mechanism of LF-induced tolerance was inhibiting maturation and function of DC and inducing the formation of regulatory T-cell subtype by "suppressor DCs" to achieve a new immune balance.
Xia
Xiaoping
X
Department of Ophthalmology, 3rd Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Zhang
Xiao
X
Huang
Xuyan
X
Li
Mu
M
Zhao
Lina
L
Tian
Donghua
D
Zhong
Robert
R
Min
Wei-Ping
WP
D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology; D060908:CTLA-4 Antigen; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D006146:Guanidines / Q000494:pharmacology*; D007108:Immune Tolerance; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010641:Phenotype; D015375:Receptors, Interleukin-2 / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology
D015703:Antigens, CD; D000943:Antigens, Differentiation; D015704:CD4 Antigens; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D006146:Guanidines; D007166:Immunosuppressive Agents; C434185:LF 150195; D015375:Receptors, Interleukin-2