Interleukin-12 increases proliferation and interferon-γ production but not cytolytic activity of human antigen-specific effector memory cytotoxic T lymphocytes: Power of the effect depends on the functional avidity of the T cell and the antigen concentration

Hetty J. Bontkes*, Janneke J. Ruizendaal, Duco Kramer, Chris J.L.M. Meijer, Marco W.J. Schreurs, Erik Hooijberg

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Cytotoxic T lymphocytes (CTLs) play an important role in the defense against viral infections and malignant diseases. Interleukin (IL)-12 plays a crucial role in induction of antigen-specific primary CTL responses and enhances proliferation, interferon-γ (IFN-γ) production, and cytolytic activity of mitogen-stimulated T cells. However, the effects of IL-12 on proliferation and effector functions of previously in vitro or in vivo primed antigen-specific CTLs are less clear. Our results show that IL-12 induces an increase in proliferation of and IFN-γ production by influenza peptide-specific CTLs, but no increase in cytolytic activity on a per cell basis was observed in bulk cultures. Stimulation of a CTL clone confirmed these results; IL-12 supported an increase in IFN-γ production, but did not increase cytolytic activity. The extent of the effect of IL-12 on IFN-γ production differs per CTL clone and depends on the avidity of the clone and the peptide concentration on its target. Our data suggest that IL-12 is a good adjuvant for boosting CTL responses, in terms of proliferation and IFN-γ production, the latter particularly for CTLs with low to intermediate avidity, such as tumor-associated self-antigen-specific CTLs.

Original languageEnglish
Pages (from-to)1137-1145
Number of pages9
JournalHuman Immunology
Volume66
Issue number11
DOIs
Publication statusPublished - 1 Nov 2005

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