Pentoxifylline inhibits granzyme B and perforin expression following T-lymphocyte activation by anti-CD3 antibody

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Résumé

Pentoxifylline (PTX), a methylxanthine derivative, is known to inhibit the production of the Th1 cytokines interleukin-2, tumour necrosis factor-α and interferon-γ. Because these cytokines play an important role in promoting the development of cell-mediated immunity, we hypothesized that PTX would also interfere with the generation of cytotoxic effector cells in response to an immunological stimulus. In this study we used a mouse model system to investigate the effect of PTX on the induction of non-specific killer lymphocytes by anti-CD3 monoclonal antibody. Anti-CD3-induced T-cell proliferation and the generation of anti-CD3-activated killer (AK) cells was inhibited in a dose-dependent fashion by PTX (25-100 μg/ml). The inhibitory effect of PTX could not be attributed to a defect in the recognition/adhesion phase of cytolysis because AK cells generated in the presence of PTX conjugated normally with P815 tumour target cells. However, AK cell expression of the cytoplasmic granule-associated cytolytic effector molecules granzyme B and perforin was markedly reduced when AK cells were induced in the presence of PTX. In contrast, PTX had no effect on AK cell expression of Fas ligand, a cell-surface cytolytic effector molecule which is involved in granule-independent cytotoxicity. PTX thus has a profound inhibitory effect in vitro on the induction of granule-dependent cytolytic effector mechanisms in a mouse model system.

Langue d'origineEnglish
Pages (de-à)623-631
Nombre de pages9
JournalInternational Journal of Immunopharmacology
Volume18
Numéro de publication11
DOI
Statut de publicationPublished - nov. 1996

Note bibliographique

Funding Information:
Acknowledyements--This work was supported by a grant to D.W.H. from the Natural Sciences and Engineering Council of Canada. A.P.M. is the recipient of a Natural Sciences and Engineering Council of Canada Postgraduate Studentship.

ASJC Scopus Subject Areas

  • Immunology
  • Pharmacology

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