Rituximab-induced direct inhibition of T-cell activation

Cancer Immunol Immunother. 2012 Aug;61(8):1233-41. doi: 10.1007/s00262-011-1168-2. Epub 2012 Jan 17.


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/m(2) 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(+)CD20(dim) 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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged, 80 and over
  • Antibodies, Monoclonal, Murine-Derived / adverse effects*
  • Antineoplastic Agents / adverse effects*
  • Cell Separation
  • Cytokines / biosynthesis
  • Female
  • Flow Cytometry
  • Humans
  • Lymphocyte Activation / drug effects*
  • Lymphocyte Activation / immunology
  • Lymphocyte Culture Test, Mixed
  • Lymphoma, Non-Hodgkin / drug therapy*
  • Lymphoma, Non-Hodgkin / immunology*
  • Male
  • Middle Aged
  • Rituximab
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / immunology


  • Antibodies, Monoclonal, Murine-Derived
  • Antineoplastic Agents
  • Cytokines
  • Rituximab