Prevention of anergy induction in cloned T cells by interleukin 12.
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)
Becker
J C
JC
Department of Dermatology, University of Würzburg, Germany.
Bröcker
E B
EB
D018122:B7-1 Antigen / Q000096:biosynthesis / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002478:Cells, Cultured; D002999:Clone Cells; D018076:DNA, Complementary / Q000235:genetics; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects*; D018664:Interleukin-12 / Q000494:pharmacology*; D008213:Lymphocyte Activation; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects* / Q000276:immunology; D008545:Melanoma / Q000473:pathology; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000494:pharmacology; D014162:Transfection; D014407:Tumor Cells, Cultured
D018122:B7-1 Antigen; D018076:DNA, Complementary; D011994:Recombinant Proteins; D018664:Interleukin-12