Generation of HSP60-specific regulatory T cell and effect on atherosclerosis.
Although CD4(+)CD25(+) regulatory T cells are pivotal in the suppression of autoimmunity, little is known about the effect of antigen-specific regulatory T cells on the formation of atheromatous plaques. Here, we describe the induction of heat-shock protein 60 (HSP60)-specific CD4(+)CD25(high) T cells by rapamycin (RPM)-treated immature dendritic cells in vitro and explore their effect on plaques in apolipoprotein E-deficient mice. Rapamycin-treated bone marrow-derived dendritic cells (DC) were immature, expressing a low level of co-stimulation factors CD86 and CD80. Naive CD4(+) T cells expressed high levels of CD25 and forkhead box P3 (Foxp3) after incubation with rapamycin-treated and HSP60-loaded DC and displayed moderate antigen-specific, IL-10-independent inhibitory function in vitro. After adoptive transfer, HSP60-specific CD4(+)CD25(high) T cells inhibited the formation of plaques, while ovalbumin-specific cells did not. These findings suggest that RPM-treated DC can induce antigen-specific CD4(+)CD25(high) Treg cells that have inhibitory activity in vitro and prevent the development of plaques in vivo.
Yang
Keping
K
Department of Cardiology, Institute of Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, PR China.
Li
Dazhu
D
Luo
Minghua
M
Hu
Yingfeng
Y
D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D050197:Atherosclerosis / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D002454:Cell Differentiation; D018834:Chaperonin 60 / Q000378:metabolism*; D003713:Dendritic Cells / Q000502:physiology; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020123:Sirolimus / Q000494:pharmacology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism*
D001057:Apolipoproteins E; D018834:Chaperonin 60; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; D020123:Sirolimus