An elevated level of IL-10- and TGFbeta-secreting T cells, B cells and macrophages in the synovial membrane of patients with reactive arthritis compared to rheumatoid arthritis.
A relative high secretion level of IL-10 and a low secretion of TNF-alpha has been described in the synovial fluid and peripheral blood of patients with reactive arthritis (ReA), possibly contributing to the persistence of bacteria. The role of TGF-beta is less clear. We investigated these cytokines in the synovial membrane of patients with ReA and rheumatoid arthritis (RA) and tried to identify their cellular source. We used sections from the synovial membrane of 4 ReA and 4 RA patients which were double stained with immunofluorescence antibodies against cell surface markers for T cells (CD3), macrophages (CD68) and B cells (CD20) in combination with antibodies against intracellular cytokines TNF-alpha, IFN-gamma, TGF-beta, IL-4 and IL-10, and quantified these using a fluorescence microscope. A lower number of TNF-alpha-secreting cells were found in ReA compared to RA: CD3+: 1.78 +/- 0.54% versus 5.02% +/- 0.47% (p = 0.034). CD68+: 2.86 +/- 0.52 versus 5.37 +/- 0.53% (p = 0.034), CD20+ : 3.02 +/- 0.42% versus 3.58 +/- 0.48% (p > 0.05). A higher number of IL-10 positive cells were found in ReA compared to RA: CD3+: 3.27 +/- 1.5% versus 1.13 +/- 0.50% (p = 0.034), CD68+ 1.23 +/- 0.75% versus 0.83 +/- 0.35% (p > 0.05), CD20+: 3.70 +/- 1.6% versus 1.6 +/- 1.1% (p > 0.05). A difference between ReA and RA was also found for TGF-beta+ T cells: CD3+ 7.86 + 1.5% versus 1.78 + 0.35% (p = 0.032); CD20+: 7.91 + 2.1% versus 2.1 + 2.8% (p > 0.05), CD68+: 7.81% + 1.24% versus 2.12 + 0.28% (p = 0.032). In conclusion, we saw a different cytokine secretion pattern in the synovial membrane of ReA and RA. For T cells in ReA we found a cytokine secretion profile typical for T regulatory cells 1 (Tr1), with an elevated level of IL-10- and TGF-beta-secreting cells. Whether this is due to a more general difference in TNF-alpha, IL-10 or TGF-beta production which is genetically determined or regulated by T cells remains to be determined.
Appel
Heiner
H
Department of Rheumatology, Charité Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200, Germany. appel@medizin.fu-berlin.de
Neure
Lucia
L
Kuhne
Maren
M
Braun
Jürgen
J
Rudwaleit
Martin
M
Sieper
Joachim
J
D015703:Antigens, CD / Q000378:metabolism; D001170:Arthritis, Infectious / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology; D002452:Cell Count; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016753:Interleukin-10 / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism* / Q000473:pathology; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D008297:Male; D000091402:Prohibitins; D013583:Synovial Membrane / Q000378:metabolism* / Q000473:pathology; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000378:metabolism
D015703:Antigens, CD; D016207:Cytokines; C000717331:PHB2 protein, human; D000091402:Prohibitins; D016212:Transforming Growth Factor beta; D016753:Interleukin-10