Contrary roles of IL-4 and IL-12 on IL-10 production and proliferation of human tumour reactive T cells.
The cytokine profile of tumour reactive T cells is likely to play a central role in their function. However, little is known about how cytokine patterns of tumour reactive T cells can be regulated. Here, the authors investigated the influence of exogenous regulatory cytokines in addition to interleukin-2 (IL-2) on cytokine patterns and the proliferation of T cells recognizing an autologous sarcoma cell line. In this system, IL-4 and IL-12 showed the most polarizing influences on tumour reactive T cells. Exogenous IL-4 induced a predominant production of IL-4 while decreasing the interferon-gamma (IFN-gamma) and IL-10 production by tumour reactive T cells. It also stimulated the growth of tumour reactive CD4+ T cell clones. In contrast, IL-12 substantially increased the production of IL-10 and IFN-gamma. This was accompanied by a growth inhibition of tumour reactive T cells. The growth of CD4+ tumour reactive T cells was also suppressed by exogenous IL-10. This study shows that cytokine patterns and proliferation tumour reactive T cells can be significantly influenced by exogenous cytokines and confirms the hypothesis of a negative feedback loop of IL-12 by the induction of IL-10 in the context of human tumour reactive T cells.
Heike
M
M
I. Medizinische Klinik und Poliklinik, Johannes-Gutenberg-Universität, Mainz, Germany.
Schlaak
J
J
Heyl
S
S
Schulze-Bergkamen
H
H
Schmitt
U
U
Meyer zum Büschenfelde
K H
KH
D015703:Antigens, CD / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D002999:Clone Cells / Q000276:immunology; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000494:pharmacology; D016753:Interleukin-10 / Q000096:biosynthesis*; D018664:Interleukin-12 / Q000494:pharmacology* / Q000502:physiology*; D015847:Interleukin-4 / Q000494:pharmacology* / Q000502:physiology*; D008213:Lymphocyte Activation; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology; D012509:Sarcoma / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000494:pharmacology
D015703:Antigens, CD; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma