title: Rituximab-induced direct inhibition of T-cell activation.
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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Hematology and Bone Marrow Transplantation, Rambam Health Care Campus, Haifa, Israel.
authors.forename: Dina
authors.initials: D
authors.lastname: Stroopinsky
authors.forename: Tamar
authors.initials: T
authors.lastname: Katz
authors.forename: Jacob M
authors.initials: JM
authors.lastname: Rowe
authors.forename: Doron
authors.initials: D
authors.lastname: Melamed
authors.forename: Irit
authors.initials: I
authors.lastname: Avivi
mesh_terms: D000328:Adult; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000009:adverse effects*; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002469:Cell Separation; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D000069283:Rituximab; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D016207:Cytokines; D000069283:Rituximab