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J Clin Immunol. 2009 Jul;29(4):479-89. doi: 10.1007/s10875-009-9282-z. Epub 2009 Mar 4.

Abatacept does not induce direct gene expression changes in antigen-presenting cells.

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  • 1Discovery Biology, Bristol-Myers Squibb, Princeton, NJ, USA.



It has been proposed that ligation of CD80 and CD86 induces reverse signaling into antigen-presenting cells. In this study, we tested the ability of abatacept, a soluble human fusion protein comprising the extracellular domain of cytotoxic T lymphocyte antigen 4 and a fragment of the Fc domain of IgG(1), to activate antigen-presenting cells by measuring changes in global transcriptional responses.


Affymetrix chips were used to measure gene expression levels using mRNA isolated from immature and mature human dendritic cells and a B cell line following 6 h of treatment with abatacept.


In contrast to robust transcriptional responses induced by the control treatment phorbol-12-myristate-13-acetate, abatacept induced minimal gene changes in three different populations of antigen-presenting cells. Furthermore, no gene changes were observed in response to belatacept, a modified version of abatacept that binds with higher avidity to CD80 and CD86.


We conclude that reverse signaling in antigen-presenting cells is unlikely to occur in response to either abatacept or belatacept, thereby supporting the modulation of CD28 signaling on T cells as the main mechanism of action for these therapeutics.

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