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Abatacept Does Not Induce Direct Gene Expression Changes in Antigen-Presenting Cells

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Abstract

Background

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 IgG1, to activate antigen-presenting cells by measuring changes in global transcriptional responses.

Methods

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.

Results

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.

Conclusions

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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Authors and Affiliations

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

    Julie A. Carman, Patricia M. Davis, Suzanne J. Suchard & Steven G. Nadler

  2. Applied Genomics, Bristol-Myers Squibb, Hopewell, NJ, USA

    Wen-Pin Yang, Jun Zhu, Han Chang, Aiqing He & Amy Truong

  3. Bristol-Myers Squibb, P.O. Box 4000, mail code K24-03, Princeton, NJ, 08543-4000, USA

    Julie A. Carman

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  1. Julie A. Carman
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  2. Patricia M. Davis
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Correspondence to Julie A. Carman.

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Carman, J.A., Davis, P.M., Yang, WP. et al. Abatacept Does Not Induce Direct Gene Expression Changes in Antigen-Presenting Cells. J Clin Immunol 29, 479–489 (2009). https://doi.org/10.1007/s10875-009-9282-z

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  • DOI: https://doi.org/10.1007/s10875-009-9282-z

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