FOXP3 gene expression in a tuberculosis case contact study.
Regulatory T lymphocytes (T(regs)) that express FOXP3 are involved in the beneficial attenuation of immunopathology, but are also implicated in down-regulation of protective responses to infection. Their role in tuberculosis (TB) is unknown. We classified 1272 healthy TB contacts according to their tuberculin skin test (TST) and interferon (IFN)-gamma enzyme-linked immunospot (ELISPOT) results and 128 TB cases, and studied the expression of FOXP3 and interleukin (IL)-10 in blood samples. Compared to the uninfected contact group (TST(-), ELISPOT(-)), we observed higher levels of FOXP3 mRNA in blood from TB patients (< 0.001), but IL-10 expression was slightly lower (P = 0.04). In contrast, FOXP3 expression levels were significantly lower (P = 0.001) in the recently infected contacts (TST(+), ELISPOT(+)) but there was no difference for IL-10 (P = 0.74). We hypothesize that during early/subclinical TB, most of which will become latent, FOXP3(+) T(regs) may be sequestered in the lungs, but when TB becomes progressive, FOXP3 reappears at increased levels in the periphery. While these findings do not reveal the role, beneficial or harmful, of T(regs) in TB, they emphasize the probable importance of these cells.
Burl
S
S
Tuberculosis Division, Bacterial Diseases Programme, Medical Research Council (UK) Unit, Banjul, The Gambia, West Africa.
Hill
P C
PC
Jeffries
D J
DJ
Holland
M J
MJ
Fox
A
A
Lugos
M D
MD
Adegbola
R A
RA
Rook
G A
GA
Zumla
A
A
McAdam
K P W J
KP
Brookes
R H
RH
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D016358:Contact Tracing; D018450:Disease Progression; D005260:Female; D051858:Forkhead Transcription Factors / Q000097:blood* / Q000235:genetics; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D007223:Infant; D016753:Interleukin-10 / Q000097:blood / Q000235:genetics; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014374:Tuberculin Test; D014376:Tuberculosis / Q000276:immunology* / Q000635:transmission
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D012333:RNA, Messenger; D016753:Interleukin-10