Browse by author
Lookup NU author(s): Alistair Brown, Dr Prakash Patel, Professor Jaap Van Laar, Professor John IsaacsORCiD
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
We previously demonstrated prolonged, profound CD4(+) T-lymphopenia in rheumatoid arthritis ( RA) patients following lymphocyte- depleting therapy. Poor reconstitution could result either from reduced de novo T-cell production through the thymus or from poor peripheral expansion of residual T-cells. Interleukin-7 (IL-7) is known to stimulate the thymus to produce new T-cells and to allow circulating mature T-cells to expand, thereby playing a critical role in T-cell homeostasis. In the present study we demonstrated reduced levels of circulating IL-7 in a cross-section of RA patients. IL-7 production by bone marrow stromal cell cultures was also compromised in RA. To investigate whether such an IL-7 deficiency could account for the prolonged lymphopenia observed in RA following therapeutic lymphodepletion, we compared RA patients and patients with solid cancers treated with high-dose chemotherapy and autologous progenitor cell rescue. Chemotherapy rendered all patients similarly lymphopenic, but this was sustained in RA patients at 12 months, as compared with the reconstitution that occurred in cancer patients by 3 - 4 months. Both cohorts produced naive T-cells containing T-cell receptor excision circles. The main distinguishing feature between the groups was a failure to expand peripheral T-cells in RA, particularly memory cells during the first 3 months after treatment. Most importantly, there was no increase in serum IL-7 levels in RA, as compared with a fourfold rise in non-RA control individuals at the time of lymphopenia. Our data therefore suggest that RA patients are relatively IL-7 deficient and that this deficiency is likely to be an important contributing factor to poor early T-cell reconstitution in RA following therapeutic lymphodepletion. Furthermore, in RA patients with stable, well controlled disease, IL-7 levels were positively correlated with the T-cell receptor excision circle content of CD4(+) T-cells, demonstrating a direct effect of IL-7 on thymic activity in this cohort.
Author(s): Ponchel F, Verburg RJ, Bingham SJ, Brown AK, Moore J, Protheroe A, Short K, Lawson CA, Morgan AW, Quinn M, Buch M, Field SL, Maltby SL, Masurel A, Douglas SH, Straszynski L, Fearon U, Veale DJ, Patel P, McGonagle D, Snowden J, Markham AF, Ma D, van Laar JM, Papadaki HA, Emery P, Isaacs JD
Publication type: Article
Publication status: Published
Journal: Arthritis Research & Therapy
Year: 2004
Volume: 7
Issue: 1
Pages: R80-R92
ISSN (print): 1478-6354
ISSN (electronic): 1478-6362
Publisher: BioMed Central Ltd.
URL: http://dx.doi.org/10.1186/ar1452
DOI: 10.1186/ar1452
Altmetrics provided by Altmetric
