PMID- 16682617
OWN - NLM
STAT- MEDLINE
DCOM- 20060609
LR  - 20171116
IS  - 1524-4539 (Electronic)
IS  - 0009-7322 (Linking)
VI  - 113
IP  - 19
DP  - 2006 May 16
TI  - Modulation of CD4(+)CD28null T lymphocytes by tumor necrosis factor-alpha 
      blockade in patients with unstable angina.
PG  - 2272-7
AB  - BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine 
      that favors the expansion of CD4(+)CD28null T cells, an aggressive and unusual 
      proinflammatory lymphocyte subset frequently observed in patients with unstable 
      angina (UA). The purpose of the present ex vivo study was to evaluate whether 
      inflammation in patients with UA may be modulated by selective blockade of 
      TNF-alpha. METHODS AND RESULTS: Peripheral blood samples were collected from 17 
      patients with UA (Braunwald's class IIIB). CD4(+)CD28null T cells were assessed 
      by flow cytometry and expressed as a percentage of all CD4+ T cells after 24 
      hours of incubation of whole blood with and without increasing doses (0.1, 1, 10, 
      and 100 microg/mL) of infliximab, an anti-TNF-alpha monoclonal antibody. In 
      addition, CD28 expression was assessed and expressed as mean fluorescence 
      intensity (geometric mean of the CD28 fluorescence value on all CD4+ T cells). 
      CD4(+)CD28null T-cell percentage decreased from a median of 6.2% (range, 1.2% to 
      23.9%) to 4.9% (range, 1.1% to 21.9%), 4.5% (range, 1.1% to 21.6%), and 4.1% 
      (range, 0.4% to 21.4%) after incubation with 1, 10, and 100 microg/mL of 
      infliximab (P for trend=0.043). Analysis of CD28 mean fluorescence intensity 
      showed that the expression of CD28 on cell surface significantly increased after 
      incubation with increasing doses of infliximab (P for trend=0.03). CONCLUSIONS: 
      The findings of this ex vivo study show that CD4(+)CD28null T-cell expansion in 
      patients with UA may be reduced by selective TNF-alpha blockade. Further studies 
      are warranted to evaluate the clinical benefit of CD4(+)CD28null T-cell 
      modulation.
FAU - Rizzello, Vittoria
AU  - Rizzello V
AD  - Cardiology Department, Catholic University, Rome, Italy.
FAU - Liuzzo, Giovanna
AU  - Liuzzo G
FAU - Brugaletta, Salvatore
AU  - Brugaletta S
FAU - Rebuzzi, Antonio
AU  - Rebuzzi A
FAU - Biasucci, Luigi M
AU  - Biasucci LM
FAU - Crea, Filippo
AU  - Crea F
LA  - eng
PT  - Journal Article
DEP - 20060508
PL  - United States
TA  - Circulation
JT  - Circulation
JID - 0147763
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (CD28 Antigens)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - B72HH48FLU (Infliximab)
SB  - IM
MH  - Aged
MH  - Angina, Unstable/*immunology/pathology
MH  - Antibodies, Monoclonal/*pharmacology
MH  - CD28 Antigens/*analysis
MH  - CD4 Lymphocyte Count
MH  - CD4-Positive T-Lymphocytes/*drug effects/immunology
MH  - Female
MH  - Flow Cytometry
MH  - Humans
MH  - Infliximab
MH  - Male
MH  - Middle Aged
MH  - T-Lymphocyte Subsets/*drug effects/immunology
MH  - Tumor Necrosis Factor-alpha/analysis/*antagonists & inhibitors/immunology
EDAT- 2006/05/10 09:00
MHDA- 2006/06/10 09:00
CRDT- 2006/05/10 09:00
PHST- 2006/05/10 09:00 [pubmed]
PHST- 2006/06/10 09:00 [medline]
PHST- 2006/05/10 09:00 [entrez]
AID - CIRCULATIONAHA.105.588533 [pii]
AID - 10.1161/CIRCULATIONAHA.105.588533 [doi]
PST - ppublish
SO  - Circulation. 2006 May 16;113(19):2272-7. doi: 10.1161/CIRCULATIONAHA.105.588533. 
      Epub 2006 May 8.