+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

Antigen-specific transforming growth factor β-induced Treg cells, but not natural Treg cells, ameliorate autoimmune arthritis in mice by shifting the Th17/Treg cell balance from Th17 predominance to Treg cell predominance

, : Antigen-specific transforming growth factor β-induced Treg cells, but not natural Treg cells, ameliorate autoimmune arthritis in mice by shifting the Th17/Treg cell balance from Th17 predominance to Treg cell predominance. Arthritis and Rheumatism 64(8): 2548-2558

Transferred CD4+CD25+FoxP3+ Treg cells can prevent autoimmune disease, but generally fail to ameliorate established disease. This study was undertaken to compare the effects of antigen-specific Treg cells induced with interleukin-2 (IL-2) and transforming growth factor β (TGFβ) ex vivo (induced Treg [iTreg] cells) to the effects of equivalent expanded thymus-derived natural Treg (nTreg) cells on established collagen-induced arthritis (CIA). CIA was induced in DBA/1 mice by immunization with type II collagen (CII), and before or shortly after immunization, mice were treated with iTreg or nTreg cells that were generated or expanded in vitro. Clinical scores were determined. Inflammatory responses were determined by measuring the levels of anti-CII antibody in the serum and examining the histologic features of the mouse joints. The Th1/Th17-mediated autoreactive response was evaluated by determining the cytokine profile of the draining lymph node (LN) cells of the mice by flow cytometry. Following transfer, nTreg cells exhibited decreased FoxP3 and Bcl-2 expression and decreased suppressive activity, and many converted to Th17 cells. In contrast, transferred iTreg cells were more numerous, retained FoxP3 expression and their suppressive activity in the presence of IL-6, and were resistant to Th17 conversion. Notably, 10 days after the transfer of donor iTreg cells, predominance was shifted from Th17 cells to Treg cells in the draining LNs of recipient mice. These findings provide evidence that transferred TGFβ-induced iTreg cells are more stable and functional than nTreg cells in mice with established autoimmunity. Moreover, iTreg cells can have tolerogenic effects even in the presence of ongoing inflammation. The therapeutic potential of human iTreg cells in subjects with chronic, immune-mediated inflammatory diseases should be investigated.


PMID: 22605463

DOI: 10.1002/art.34513

Other references

Naveh Z., 1987: Biocybernetic and thermodynamic perspectives of landscape functions and land use patterns. This paper develops and applies two concepts which are fundamental to landscape ecology. These concepts concern biocybernetics, which is the theory of regulation of biological and ecological systems, and thermodynamics, especially the flux of ener...

Houser, J.S., 1916: Two destructive Fall Caterpillars. The caterpillars here dealt with are the walnut datana, Datana, integerrima, and the yellow-necked apple caterpillar, or apple datana, Datnna ministra, 'which attack walnut and apple trees during late summer and early autumn in all parts of t...

Kurosawa, K.; Lin, W.; Ohta, K., 2010: Distinct roles of HDAC1 and HDAC2 in transcription and recombination at the immunoglobulin loci in the chicken B cell line DT40. The class I histone deacetylases HDAC1 and HDAC2 are highly conserved except for their C-terminal domain, but are presumed to have distinct functions in various tissues. We investigated the division of roles between HDAC1 and HDAC2 for the control...

Teculescu, D.B.; Pham, Q.T., 1986: Common cold should be taken into account in epidemiological studies on pulmonary function, even in the absence of symptoms or signs. International Journal of Epidemiology 15(3): 433-434

Ozeki, H.; Shirai, S.; Nozaki, M.; Mizuno, S.; Sakurai, E.; Ikeda, K.; Ogura, Y., 1999: Systemic abnormalities associated with Peters anomaly. We reviewed 30 cases of Peters' anomaly during the past 16 years. Systemic disorders were present in 10 cases, including retarded growth 5 cases, cleft lip and/or palate 4 cases and heart anomalies 4 cases. They were aged 2.0+-1.5 months and...

Nanni, M.R.; Melcore, G.; Peroni, G.; Bissi, D., 1983: Congenital choanal atresia: presentation of a case. La Radiologia Medica 69(1-2): 61-62

Engelman, R.M.; Boyd, A.D.; Kronzon, I.; Chandra, R.; Rosenfeld, R., 1976: A comparison of the level of myo cardial ischemia produced by 3 techniques employed for coronary re vascularization. Ischemic arrest and snaring of a coronary artery, in this case the left anterior descending (LAD), were studied to measure the difference in postischemic myocardial perfusion. The results were correlated with ECG monitoring to evaluate atrioventri...

Bunka, S.W.; Potter, A.A.; Gerlach, G.F., 1998: Cloning and sequencing of the transferrin-binding protein genes of Actinobacillus pleuropneumoniae, biotype 1-serotype 5 and biotype 2-serotype 2. Abstracts of the General Meeting of the American Society for Microbiology 98: 280

Bourry, A.; Poutrel, B.; Rocourt, J., 1995: Bovine mastitis caused by Listeria monocytogenes: characteristics of natural and experimental infections. Experimental mastitis induced with a single intramammary injection of Listeria monocytogenes was compared with two naturally occurring cases. Four strains of L. monocytogenes, two of serotype 1/2a and two of serotype 4b were used for the experimen...

Gansl R.C.; Hippolito J.; Cutait R.; Souza A.H.; Nadalin W.; Habr Gama A.; Pinotti H.W., 1986: Treatment of liver metastatic colorectal carcinoma with sequential methotrexate 5 fluorouracil and external hepatic radiation. Proceedings American Society of Clinical Oncology Annual Meeting 5: 94