Elevated number of recently activated T cells in bone marrow of patients with rheumatoid arthritis: a role for interleukin 15?
OBJECTIVE
(1) To compare the absolute T-cell numbers in bone marrow (BM) isolated from patients with rheumatoid arthritis (RA) and osteoarthritis (OA); (2) to measure the levels of soluble interleukin 15 (IL-15) and IL-7; (3) to analyse the expression of activation markers on T cells; (4) to analyse influence of IL-15 stimulation on T-cell proliferation.


METHODS
BM samples were obtained from patients undergoing joint replacement surgery. Concentrations of IL-15 and IL-7 were measured using specific ELISAs. The absolute number of T lymphocytes, their activation status and proliferation were evaluated by flow cytometry.


RESULTS
BM from patients with RA contained double the number of CD3 T cells in comparison with OA (6.1 vs 2.7 × 10(6) cells/ml, p<0.008). Ratio CD3CD4:CD3CD8 was increased in RA BM, clearly indicating accumulation of CD3CD4 cells. T cells obtained from patients with RA expressed higher level of early activation markers than from OA. Elevated levels of IL-15 were found in BM plasma from patients with RA in comparison with patients with OA (1304.5±956.3 pg/ml and 760±238.7 pg/ml respectively, p<0.01). These data were confirmed by immunohistochemistry of RA BM from regions proximal and distal to the joint. Although both CD3CD4 and CD3CD8 cells proliferated after IL-15 stimulation in vitro, CD3CD4 cells from patients with RA proliferated more vigorously than those from patients with OA, reflecting the composition of T-cell subsets in BM.


CONCLUSIONS
These results suggest that locally overproduced IL-15 may be responsible for the activation and proliferation of T cells in situ, reflected by significantly increased number of activated T cells in RA BM, possibly contributing to the pathogenesis of RA.
Kuca-Warnawin
Ewa
E
Department of Pathophysiology and Immunology, Institute of Rheumatology, Warsaw, Poland. ewawarnawin@poczta.onet.pl
Burakowski
Tomasz
T
Kurowska
Weronika
W
Prochorec-Sobieszek
Monika
M
Radzikowska
Anna
A
Chorazy-Massalska
Magdalena
M
Maldyk
Pawel
P
Kontny
Ewa
E
Maslinski
Wlodzimierz
W
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D001853:Bone Marrow / Q000276:immunology*; D017252:CD3 Complex / Q000032:analysis; D016022:Case-Control Studies; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D019409:Interleukin-15 / Q000032:analysis / Q000276:immunology*; D015851:Interleukin-7 / Q000032:analysis; D008213:Lymphocyte Activation / Q000276:immunology; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D055815:Young Adult
D017252:CD3 Complex; D019409:Interleukin-15; D015851:Interleukin-7