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Updated: Aug 17, 2026
Induction of Alloantigen-specific Anergy in Human Peripheral Blood Mononuclear Cells by Alloantigen Stimulation with Co-stimulatory Signal Blockade
Published on: March 14, 2011
Prevention of anergy induction in cloned T cells by interleukin 12
1Department of Dermatology, University of Würzburg, Germany.
Abstract:
A variety of tumors are potentially immunogenic but do not stimulate an effective antitumor immune response in vivo. Tumors may be capable of delivering antigen-specific signals to T cells, but may not deliver the costimulatory signals necessary for full activation of T cells. In this regard, we recently reported that a human melanoma cell line (sMC) expressing MHC class II, was able to induce clonal anergy in a specific, MHC-restricted CD-4+ T cell clone (sTC3). We used this system to investigate the influence of interleukin (IL)-12 on induction of this T cell unresponsiveness. The presence of 10 to 100 U IL-12 during the induction phase of anergy leads to a primary proliferative response of sTC3, which was significantly higher than that induced by IL-12 alone; however, in the absence of IL-12 no proliferation was seen during the induction of anergy. Subsequent optimal stimulation of IL-12 treated cells, but not of those cultured without IL-12, led to substantial IL-2 production and cell proliferation. This indicates that induction of the unresponsive state could be inhibited by IL-12. In addition, we have recently demonstrated that anergic T cell clones can produce high amounts of IL-10 and that this event was correlated with their impaired ability to produce IL-2. This marked induction of IL-10 can be suppressed if IL-12 is present during initiation of unresponsiveness. However, IL-12 was not able to prime the T cell clone, sTC3, to become resistant against the anergizing stimulus, as this cytokine was only effective when present at the time of anergy induction.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Interleukin-12 (IL-12) can prevent T cell anergy, a state of immune unresponsiveness, in cancer. This cytokine promotes T cell proliferation and IL-2 production, crucial for effective antitumor immunity.
Area of Science:
- Immunology
- Cancer Biology
- Molecular Biology
Background:
- Tumors can evade immune detection by failing to provide necessary costimulatory signals for T cell activation.
- Tumor-induced T cell anergy, a state of functional unresponsiveness, hinders effective anti-tumor immune responses.
- A human melanoma cell line (sMC) was previously shown to induce anergy in a specific CD-4+ T cell clone (sTC3).
Purpose of the Study:
- To investigate the role of interleukin-12 (IL-12) in modulating T cell anergy induction.
- To determine if IL-12 can overcome tumor-induced T cell unresponsiveness.
Main Methods:
- Utilized a human melanoma cell line (sMC) and a specific CD-4+ T cell clone (sTC3) to model T cell anergy.
- Administered varying concentrations of IL-12 during the T cell anergy induction phase.
- Assessed T cell proliferation, IL-2 production, and IL-10 production following IL-12 treatment.
Main Results:
- IL-12 presence during anergy induction significantly enhanced T cell proliferation compared to IL-12 alone.
- IL-12 treatment enabled subsequent T cell stimulation, leading to IL-2 production and proliferation, which was not observed without IL-12.
- IL-12 suppressed the induction of IL-10 production in anergic T cells.
- IL-12 was effective only when present during the initial anergy induction, not for priming resistance.
Conclusions:
- IL-12 can inhibit the induction of T cell anergy, thereby potentially restoring anti-tumor immune responses.
- IL-12's ability to promote T cell proliferation and IL-2 production, while suppressing IL-10, is key to overcoming tumor-induced unresponsiveness.
- The timing of IL-12 administration is critical for its efficacy in preventing T cell anergy.
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