Interleukin-12 increases proliferation and interferon-gamma 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.
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-gamma (IFN-gamma) 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-gamma 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-gamma production, but did not increase cytolytic activity. The extent of the effect of IL-12 on IFN-gamma 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-gamma production, the latter particularly for CTLs with low to intermediate avidity, such as tumor-associated self-antigen-specific CTLs.
Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands. hj.bontkes@vumc.nl
Hetty J
HJ
Bontkes
Janneke J
JJ
Ruizendaal
Duco
D
Kramer
Chris J L M
CJ
Meijer
Marco W J
MW
Schreurs
Erik
E
Hooijberg
D017951:Antigen Presentation / Q000276:immunology; D002448:Cell Adhesion / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D000939:Epitopes / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis*; D018664:Interleukin-12 / Q000502:physiology*; D011485:Protein Binding / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D014763:Viral Matrix Proteins / Q000276:immunology
D000939:Epitopes; C488936:M1 protein, Influenza A virus; D014763:Viral Matrix Proteins; D018664:Interleukin-12; D007371:Interferon-gamma