Altered status of CD4(+)CD25(+) regulatory T cells in patients with acute coronary syndromes.
OBJECTIVE
Considerable evidence supports the role of innate and adaptive immunity in the progression and destabilization of the atheromatous plaque. Naturally occurring CD4(+)CD25(+) regulatory T cells (Tregs) are a subpopulation of lymphocytes that are capable of suppressing the progression of experimental autoimmune disorders. We have hypothesized that peripheral numbers and function of Tregs would be deranged in patients with acute coronary syndromes (ACS).


RESULTS
Peripheral numbers of Tregs were evaluated by FACS employing labelled antibodies to CD4 and CD25. Functional suppressive properties of Tregs were assayed by establishing a triple-cell culture in which purified Tregs were incubated with irradiated antigen-presenting cells and anti-CD3-activated responder T cells. Proliferation in the presence or absence of oxidized LDL (oxLDL) was evaluated by thymidine incorporation. mRNA and protein content of foxp3, a master transcriptional regulator of Tregs, were determined for all subjects. Patients with ACS exhibited significantly reduced numbers of peripheral Tregs as compared with patients with stable angina and normal coronary artery subjects. Moreover, oxLDL induced a more profound reduction in Treg numbers in patients with ACS. Tregs in ACS patients were significantly compromised as their ability to suppress responder CD4(+)CD25(-) T-cell proliferation was attenuated. mRNA and protein content of foxp3 were significantly reduced in purified Tregs obtained from patients with ACS.


CONCLUSIONS
In patients with ACS, naturally occurring CD4(+)CD25(+) Treg numbers are reduced and their functional properties compromised. These findings may aid in understanding the mechanisms leading to culprit plaque associated T-cell activation in patients with ACS.
Mor
Adi
A
Department of Cardiology, Tel Aviv Sourasky Medical Center, Tel Aviv University, Sackler School of Medicine, Tel Aviv 64239, Israel.
Luboshits
Galia
G
Planer
David
D
Keren
Gad
G
George
Jacob
J
D000208:Acute Disease; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D000943:Antigens, Differentiation / Q000378:metabolism; D015704:CD4 Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D060908:CTLA-4 Antigen; D003327:Coronary Disease / Q000276:immunology*; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D015704:CD4 Antigens; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein