Expression of full-length and splice forms of FoxP3 in rheumatoid arthritis.
OBJECTIVE
The aim of our study was to compare the presence of full-length and alternative splice forms of FoxP3 mRNA in CD4 cells from rheumatoid arthritis (RA) patients and healthy controls.


METHODS
A quantitative real-time polymerase chain reaction (QRT-PCR) method was used to measure the amount of FoxP3 mRNA full-length and splice forms. CD4-positive T cells were isolated from peripheral blood from 50 RA patients by immunomagnetic separation, and the FoxP3 mRNA expression was compared with the results from 10 healthy controls.


RESULTS
We observed an increased expression of full-length FoxP3 mRNA in RA patients when compared to healthy controls, as well as an increase in CD25 mRNA expression, but no corresponding increase in CTLA-4 mRNA expression. The presence of an alternative splice form of FoxP3 lacking exon 2 was confirmed in both RA patients and healthy controls, but with no significant difference in expression between the two groups. There was a positive correlation between the amount of FoxP3 mRNA and the clinical inflammation parameters C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), and a negative correlation between FoxP3 mRNA and the dose of methotrexate (MTX) given to the patients.


CONCLUSIONS
RA patients express more full-length FoxP3 than healthy controls in peripheral blood CD4-positive cells, suggesting an increased number of regulatory T cells (Tregs). However, no concomitant increase in CTLA-4 expression was seen. We therefore propose that the Tregs are left unable to suppress the ongoing inflammation due to a deficiency in CTLA-4 needed for cell contact-dependent suppression.
Ryder
L R
LR
Department of Immunology, University of Copenhagen, The Parker Institute, Frederiksberg Hospital, Rigshospitalet, Denmark. parker@frh.regionh.dk
Woetmann
A
A
Madsen
H O
HO
Ødum
N
N
Ryder
L P
LP
Bliddal
H
H
Danneskiold-Samsøe
B
B
Ribel-Madsen
S
S
Bartels
E M
EM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D012333:RNA, Messenger