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Rituximab-induced direct inhibition of T-cell activation

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Abstract

Background

Rituximab, an anti-CD20 monoclonal antibody, is reported to increase the T-cell-dependent infection risk. The current study was designed to investigate whether rituximab interferes with T-cell activation.

Patients and methods

Patients with non-Hodgkin lymphoma receiving 4–6 courses of 375 mg/m2 rituximab underwent detailed assessment of T-cell activation pre- and post-rituximab. A similar analysis assessed the in vitro effect of rituximab on T-cell activation in response to allogeneic dendritic cells (allo-DCs) and other stimuli.

Results

Patients receiving rituximab exhibited a significant decline in IL-2 and IFN-γ levels in peripheral blood, most prominent after repeated rituximab courses. Evaluation at 3 months after rituximab therapy showed restoration of inflammatory cytokine production. Similarly, in vitro stimulation of peripheral blood mononuclear cells in the presence of rituximab resulted in a significant decrease in T-cell activation markers, inflammatory cytokine production and proliferative capacity. These effects were also observed using B-cell-depleted T cells (CD3+CD25−CD19−) and were accompanied with disappearance of CD3+CD20dim T-cell population.

Conclusion

Rituximab administration results in transient, dose-dependent T-cell inactivation. This effect is obtained even in B-cell absence and may increase the infection risk.

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Acknowledgments

The research was supported in part by Roche Pharmaceuticals.

Conflict of interest

The authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Hematology and Bone Marrow Transplantation, Rambam Health Care Campus, P.O. Box 9602, 31096, Haifa, Israel

    Dina Stroopinsky, Tamar Katz, Jacob M. Rowe & Irit Avivi

  2. Bruce Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel

    Tamar Katz, Jacob M. Rowe, Doron Melamed & Irit Avivi

Authors
  1. Dina Stroopinsky
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  2. Tamar Katz
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  3. Jacob M. Rowe
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  4. Doron Melamed
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  5. Irit Avivi
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Corresponding author

Correspondence to Irit Avivi.

Additional information

Dina Stroopinsky and Tamar Katz contributed equally to this manuscript.

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Stroopinsky, D., Katz, T., Rowe, J.M. et al. Rituximab-induced direct inhibition of T-cell activation. Cancer Immunol Immunother 61, 1233–1241 (2012). https://doi.org/10.1007/s00262-011-1168-2

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  • DOI: https://doi.org/10.1007/s00262-011-1168-2

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