Abatacept decreases disease activity in a absence of CD4(+) T cells in a collagen-induced arthritis model.

Abstract

INTRODUCTION:

Abatacept is a fusion protein of human cytotoxic T-lymphocyte-associated protein (CTLA)-4 and the Fc portion of human immunoglobulin G1 (IgG1). It is believed to be effective in the treatment of rheumatoid arthritis by inhibiting costimulation of T cells via blocking CD28-B7 interactions as CTLA-4 binds to both B7.1 (CD80) and B7.2 (CD86). However, the interaction of CD28 with B7 molecules is crucial for activation of naive cells, whereas it is unclear whether the action of already activated CD4(+) T cells, which are readily present in established disease, also depends on this interaction. The aim of this study was to determine whether the mode of action of abatacept depends solely on its ability to halt T cell activation in established disease.

METHODS:

Arthritis was induced in thymectomized male DBA/1 mice by immunisation with bovine collagen type II. The mice were subsequently depleted for CD4(+) T cells. Abatacept or control treatment was started when 80 % of the mice showed signs of arthritis. Arthritis severity was monitored by clinical scoring of the paws, and anti-collagen antibody levels over time were determined by enzyme-linked immunosorbent assay.

RESULTS:

Treatment with abatacept in the absence of CD4(+) T cells resulted in lower disease activity. This was associated with decreasing levels of collagen-specific IgG1 and IgG2a antibodies, whereas the antibody levels in control or CD4(+) T cell-depleted mice increased over time.

CONCLUSIONS:

These results show that abatacept decreased disease activity in the absence of CD4(+) T cells, indicating that the mode of action of abatacept in established arthritis does not depend entirely on its effects on CD4(+) T cell activation.

• Authors: Diahann T S L Jansen, Hanane el Bannoudi, Ramon Arens, Kim L L Habets, Marjolijn Hameetman, Tom W J Huizinga, Jeroen N Stoop, René E M Toes
• Journal: Arthritis research & therapy (Arthritis Res Ther) Vol. 17 Pg. 220 (Aug 20 2015) ISSN: 1478-6362 [Electronic] England
• PMID: 26290328 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antirheumatic Agents
• Collagen Type II
• Immunoglobulin G
• Abatacept

Topics

• Abatacept (pharmacology)
• Animals
• Antirheumatic Agents (pharmacology)
• Arthritis, Experimental (chemically induced, drug therapy, immunology)
• CD4-Positive T-Lymphocytes (immunology, metabolism)
• Cattle
• Collagen Type II (immunology)
• Enzyme-Linked Immunosorbent Assay
• Immunoglobulin G (blood, immunology)
• Lymphocyte Count
• Lymphocyte Depletion (methods)
• Male
• Mice, Inbred DBA
• Severity of Illness Index
• Thymectomy
• Treatment Outcome