2337 - Antigen-Specific Regulatory Tr1 Lymphocytes As New Cell-Therapy Approach for Immunotherapy in Arthritis

Tuesday, November 8, 2011: 9:00 AM-6:00 PM
Hall F2 - Poster Hall (McCormick Place West)
Delphine Martire1, Julie Quentin1, Anne-Laure Mausset-Bonnefont1, Helène Asgnali2, Nathalie Belmonte2, Arnaud Foussat2, Christian Jorgensen3 and Pascale Louis-Plence1, 1Inserm U844, Montpellier, France, 2TxCell, Valbonne-Sophia Antipolis, France, 3CHU Lapeyronie, Montpellier, France
Presentation Number: 2337

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).

Method: 

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 10x106, 3x106, 1x106, 0.3x106 of 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.

Result: 

One single injection of 3x106 or 1x106 of 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 0.3x 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 3x106and 1x106 of 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 3x106, 1x106 of 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).


Keywords: T cells, cell biology and regulatory cells

Disclosure: D. Martire, None; J. Quentin, None; A. L. Mausset-Bonnefont, None; H. Asgnali, None; N. Belmonte, None; A. Foussat, None; C. Jorgensen, None; P. Louis-Plence, None.