T Cell-Dependent B Cell Lymphoproliferation and Activation Induced by the Drug Diphenylhydantoin

  • Helga Gleichmann
  • Steven Pals
  • Thaddaus Radaszkiewicz
  • Martin Wasser
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 149)


A number of adverse effects can occur in patients receiving the anti-epileptic drug diphenylhydantoin (DPH), such as development of lymphadenopathy, lymphoma and formation of various autoantibodies (1,2). To date, the pathogenetic mechanism(s) underlying the induction of this wide spectrum of immunopathological symptoms is unknown. Interestingly, many of these DPH induced lesions also develop as sequelae of graft-versus-host reactions (GVHR) in animal models and man. In the murine GVHR the various pathological disorders of the F1 recipients are initiated by alloreactive parental T lymphocytes (1,2). Based on these observations and the experimental data on T cell activation by “altered-self” structures on lymphoid cells, it has been postulated that the pathological symptoms observed in patients sensitized to DPH may result from GVH-like reactions of T lymphocytes stimulated by autologous lymphoid cells, which were rendered “non-self” by DPH. This extended the original concept of Allison et al. (3) on abnormal interactions of T and B lymphocytes in the induction of autoantibody formation. Results obtained by means of the popliteal lymph node (PLN) assay in mice support this concept (4).


Lymphoid Cell Popliteal Lymph Node Pathological Disorder Pathological Symptom Positive Lymphocyte 
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Copyright information

© Plenum Press, New York 1982

Authors and Affiliations

  • Helga Gleichmann
    • 1
  • Steven Pals
    • 2
  • Thaddaus Radaszkiewicz
    • 2
  • Martin Wasser
    • 3
  1. 1.Department of ImmunologyThe Netherlands Cancer InstituteAmsterdamThe Netherlands
  2. 2.Department of Immunohistopathology, Central Laboratory of the Netherlands Red Cross Blood Transfusion Service and Laboratory of Experimental and Clinical Immunology of the University of AmsterdamAmsterdamThe Netherlands
  3. 3.Medical StudentThe Netherlands

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