Contrary Roles of IL‐4 and IL‐12 on IL‐10 Production and Proliferation of Human Tumour Reactive T Cells

Abstract

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-g (IFN-g) 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-g. 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.

Characteristic Cytokine Products of Th1 and Th2 Cells in Hemodialysis Patients

“…The striking difference in IFN-γ and IL-2 gene expressions indicates that these cytokines are under separate control. Moreover, IL-12 is a potent stimulus for IFN-γ secretion by NK cells [48, 49]. IFN-γ then stimulates macrophage activation which among numerous responses includes increased cytokine synthesis, ultimately leading to even more NK cell IFN-γ production [50].…”

Differential expression of IFN-γ, IL-4, IL-10, and IL-1β mRNAs in decalcified tissue sections of mouse lipopolysaccharide-induced periodontitis mandibles assessed by in situ hybridization

“…IL-4 can inhibit a variety of IFN-γ functions (Heike et al 1997;Tipping et al 1997) as well as the synthesis of proinflammatory cytokines such as IL-1β, TNF-α, and IL-6 by monocytes/macrophages (Essner et al 1989;Hart et al 1989;Te Velde et al 1990). Considering that the inflammation shifted to the chronic phase in the late experimental period, Th2 may regulate inflammatory events, including bone resorption, in the late phase of this model, but not in the early phase.…”

Targeted therapy of solid malignancies via HLA class II antigens: a new biotherapeutic approach?

“…Emerging experimental evidences indicate that HLA-DR antigens expressed on neoplastic cells can play an important role in tumor immunology, and that alterations in their levels of expression might affect tumor immune escape (Heike et al, 1996;Byrne and Halliday, 2003). Based on this idea, different studies have focused on the prognostic value of HLA-DR antigens expression on solid malignancies; however, the results obtained so far are still contradictory.…”

“…In this regard, experimental findings have shown that selected tumor-associated antigens (TAA) are effectively presented by HLA class II antigens to CD4 þ T cells (Renkvist et al, 2001;Tatsumi et al, 2003). Furthermore, it has been demonstrated that solid tumor cells can themselves act as nonprofessional APC being directly able to stimulate the proliferation of autologous CD4 þ T cells (Heike et al, 1996). However, it has also been suggested that tumor cells drive T cells in an anergy state that results in immunosuppression of tumor-reactive T-cell clones (Byrne and Halliday, 2003).…”