Role of naturally occurring CD4+ CD25+ regulatory T cells in experimental atherosclerosis.
OBJECTIVE
Naturally occurring CD4+ CD25+ regulatory T cells (Tregs) exert suppressive effects on effector CD4 cells and downregulate experimental autoimmune disorders. We investigated the importance and potential role of Tregs in murine atherogenesis.


RESULTS
Tregs were investigated comparatively between aged and young apolipoprotein E-knockout (ApoE-KO) mice and age-matched C57BL/6 littermates. The effect of oxidized LDL (oxLDL) was tested on the functional suppressive properties of Tregs from ApoE-KO and C57BL/6 mice. Tregs, CD4+ CD25- cells, and saline were infused into ApoE-KO mice to study their effects on atherogenesis. Treg numbers were reduced in atherosclerotic compared with nonatherosclerotic ApoE-KO mice. The functional suppressive properties of Tregs from ApoE-KO mice were compromised in comparison with those from their C57BL/6 littermates. Thus, oxLDL attenuated the suppressive properties of Tregs from C57BL/6 mice and more so in ApoE-KO mice. Transfer of Tregs from age-matched ApoE-KO mice resulted in significant attenuation of atherosclerosis compared with that after delivery of CD4+ CD25+/- T cells or phosphate-buffered saline.


CONCLUSIONS
CD4+ CD25+ Tregs may play a protective role in the progression of atherosclerosis and could be considered a therapeutic tool if results from human studies can solidify observations in murine models.
Mor
Adi
A
Department of Cardiology, Tel Aviv Sourasky Medical Center, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
Planer
David
D
Luboshits
Galia
G
Afek
Arnon
A
Metzger
Shula
S
Chajek-Shaul
Tova
T
Keren
Gad
G
George
Jacob
J
D000375:Aging; D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency*; D050197:Atherosclerosis / Q000209:etiology* / Q000473:pathology* / Q000517:prevention & control; D015153:Blotting, Western; D002478:Cells, Cultured; D018920:Coculture Techniques; D018450:Disease Progression; D015536:Down-Regulation; D051858:Forkhead Transcription Factors / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics; D053645:Interleukin-2 Receptor alpha Subunit / Q000172:deficiency / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000378:metabolism; D012850:Sinus of Valsalva / Q000378:metabolism / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology / Q000637:transplantation
D001057:Apolipoproteins E; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; D008077:Lipoproteins, LDL; D012333:RNA, Messenger; C099252:oxidized low density lipoprotein; D016753:Interleukin-10