TY - JOUR
T1 - Interleukin-12 increases proliferation and interferon-γ production but not cytolytic activity of human antigen-specific effector memory cytotoxic T lymphocytes
T2 - Power of the effect depends on the functional avidity of the T cell and the antigen concentration
AU - Bontkes, Hetty J.
AU - Ruizendaal, Janneke J.
AU - Kramer, Duco
AU - Meijer, Chris J.L.M.
AU - Schreurs, Marco W.J.
AU - Hooijberg, Erik
PY - 2005/11/1
Y1 - 2005/11/1
N2 - 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.
AB - 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.
KW - Avidity
KW - Cytotoxic T lymphocyte
KW - Interferon-γ
KW - Interleukin-12
KW - Vaccination
UR - http://www.scopus.com/inward/record.url?scp=33645241423&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.humimm.2006.02.002
DO - https://doi.org/10.1016/j.humimm.2006.02.002
M3 - Article
C2 - 16571414
SN - 0198-8859
VL - 66
SP - 1137
EP - 1145
JO - Human immunology
JF - Human immunology
IS - 11
ER -