Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.


Antigen-Specific Regulatory Tr1 Lymphocytes As New Cell-Therapy Approach for Immunotherapy in Arthritis.

Martire1,  Delphine, Quentin1,  Julie, Mausset-Bonnefont1,  Anne-Laure, Asgnali2,  Helène, Belmonte2,  Nathalie, Foussat2,  Arnaud, Jorgensen3,  Christian

Inserm U844, Montpellier, France
TxCell, Valbonne-Sophia Antipolis, France
CHU Lapeyronie, Montpellier, France

Background/Purpose:

Tr1 cells have been characterized as induced T regulatory lymphocytes (Treg) inhibiting inflammation in various chronic inflammatory models. Based on these data, a Phase I/II clinical trial is currently under investigation in Crohn's disease (TxCell). However, the therapeutic potential of these cells has not yet been evaluated in rheumatoid arthritis. In this study, we investigated the therapeutic potential of bovine type II collagen-(bCII) specific Tr1 cells, isolated from TBC mice, in the experimental model of collagen-induced arthritis (CIA).

Methods:

Collagen type II specific Tr1 clones were obtained from TCR transgenic mice and expanded in vitro. Selected clones showed in vitro antigen specificity, Tr1 cytokine profile (IL10high/IL4neg) and IL10- and TGFb-dependent suppressive activity. Male DBA/1 mice were immunized with bovine type II collagen (bCII) and 10×106, 3×106, 1×106, 0.3×106of Tr1 cells were injected (i.v) 28 days post-immunization. Hind paws swelling and clinical signs of arthritis were scored, as well as biological parameters such as the level of anti-bCII antibodies in the sera of treated mice and the cytokine profile of bCII specific T cells.

Results:

One single injection of 3×106 or 1×106of Tr1 cells at day 28, in ongoing arthritis, significantly inhibits the development of arthritic disease, shown by reduction of disease severity and incidence. In contrast the injection of 0.3× 106 and 10M of Tr1 cells did not improve the clinical signs of arthritis. The analysis of the bCII specific T cell responses following euthanasia of the mice injected with 3×106and 1×106of Tr1 cells revealed a decrease of proliferation of bCII specific T cells and a slight increase of IL-10 secreted by activated splenocytes. The protection of the mice was associated with a decrease of anti bCII specific antibodies in the sera,.

Importantly, these preliminary data indicate that a single injection of Tr1 cells at disease onset could reduce disease severity and incidence in experimental arthritis.

Conclusion:

Single dose 3×106, 1×106of Tr1 cell administration showed a reduction of disease incidence and severity in CIA demonstrating the therapeutic potential of Tr1 cells in arthritis. A phase I/II clinical trial is ongoing in Rheumatoid Arthritis patient in France (TxCELL, France).

To cite this abstract, please use the following information:
Martire, Delphine, Quentin, Julie, Mausset-Bonnefont, Anne-Laure, Asgnali, Helène, Belmonte, Nathalie, Foussat, Arnaud, et al; Antigen-Specific Regulatory Tr1 Lymphocytes As New Cell-Therapy Approach for Immunotherapy in Arthritis. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :2337
DOI:

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