Author: M. Margarida Souto-Carneiro ; Lina Carvalho ; Bruno R. Raposo ; José A. Pereira da Silva ; Helena Carvalheiro ; Luis Graça ; Ana M. Água-Doce ; Paulo Rodrigues-Santos

AbstractObjectiveCD8+ T cells are part of the T cell pool infiltrating the synovium in rheumatoid arthritis (RA). However, their role in the pathogenesis of RA has not been fully delineated. Using the K/BxN mouse model of spontaneous chronic arthritis, which shares many similarities with RA, we studied the potential of CD8+ T cell depletion with monoclonal antibodies (mAb) to stop and reverse the progression of experimental arthritis.MethodsCD8+ T cells from the blood and articular infiltrate of K/BxN mice were characterized for cell surface phenotypic markers and for cytokine production. Additionally, mice were treated with specific anti‐CD8 mAb (YTS105 and YTS169.4), with and without thymectomy.ResultsCD8+ T cells from the peripheral blood and joints of K/BxN mice were mainly CD69+ and CD62L−CD27+ T cells expressing proinflammatory cytokines (interferon‐γ [IFNγ], tumor necrosis factor α [TNFα], interleukin‐17a [IL‐17A], and IL‐4), and granzyme B. In mice receiving anti‐CD8 mAb, the arthritis score improved 5 days after treatment. Recovery of the CD8+ T cells was associated with a new increase in the arthritis score after 20 days. In thymectomized and anti‐CD8 mAb–treated mice, the arthritis score improved permanently. Histologic analysis showed an absence of inflammatory infiltrate in the anti‐CD8 mAb–treated mice. In anti‐CD8 mAb–treated mice, the serologic levels of TNFα, IFNγ, IL‐6, and IL‐5 normalized. The levels of the disease‐related anti–glucose‐6‐phosphate isomerase antibodies did not change.ConclusionThese results indicate that synovial activated effector CD8+ T cells locally synthesize proinflammatory cytokines (IFNγ, TNFα, IL‐17, IL‐6) and granzyme B in the arthritic joint, thus playing a pivotal role in maintaining chronic synovitis in the K/BxN mouse model of arthritis.

01 Dec 1998·European Journal of ImmunologyQ3 · MEDICINE

Thymus-dependent monoclonal antibody-induced protection from transferred diabetes

Q3 · MEDICINE

Article

Author: Silvia Zusman Harach ; Jenny M. Phillips ; Nicole M. Parish ; Laura Bowie ; Anne Cooke

It is well established that long-term protection from insulin-dependent diabetes mellitus (IDDM) can be afforded to non-obese diabetic (NOD) mice by a short course of non-depleting (nd) anti-CD4 monoclonal antibodies (mAb). Since it is increasingly apparent that the CD8+ T cell plays a prominent role in the development of IDDM, we have investigated the effect of an anti-CD8 mAb (YTS 105) of the same isotype in both spontaneous and induced IDDM in NOD mice. Treatment with YTS 105 for 3 weeks was able to prevent the transfer of IDDM for a long period, and also substantially reduced spontaneous IDDM in female NOD mice. The role of the thymus in tolerance induction by these antibodies was studied. In the adult transfer model, thymectomized NOD mice, unlike their euthymic counterparts, were not protected long-term by treatment with YTS 105, and began to become overtly diabetic shortly after treatment. This was also true when the nd anti-CD4 mAb was used. Protection from spontaneous disease was not affected in the same way by thymectomy. The reasons for the observed effect of the thymus in the transfer model, and the differences between the two models that may explain the contrasting results are discussed.

100 Deals associated with YTS-105

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Mesothelioma	Phase 1	CN	BriSTAR Immunotech LimitedStartup	-
Pancreatic Cancer	Phase 1	CN	BriSTAR Immunotech LimitedStartup	-

Clinical Result

Indication

Phase

Evaluation

View All Results

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis


No Data

YTS-105

Overview

Basic Info

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation