Autologous killing by a population of intermediate T‐cell receptor cells and its NK1.1⁺ and NK1.1⁻ subsets, using Fas ligand/Fas molecules

Abstract

SUMMARYSelf-reactive clones, estimated by anti-Vb monoclonal antibodies (mAb) in conjunction with the Mls system, are confined to a population of intermediate (int) T-cell receptor ( TCR) (or CD3) cells (i.e. TCRint cells), but are not found among TCRhigh cells. The next questions to be answered are whether autologous killing is confined to TCRint cells and how such killing is mediated. In this study, 51Cr-labelled thymocytes of syngeneic or allogeneic origin were used as target cells (4-hr assay). When liver and splenic mononuclear cells (MNC ) obtained from B6 mice were used as eÂector cells, prominent autologous killing was seen in liver MNC, but not splenic MNC. Such killing was not seen when thymocytes from B6-lpr/lpr mice (i.e. Fas−) were used as target cells, nor when liver MNC from MRL-gld/gld mice (i.e. Fas ligand−) were used as eÂector cells (target thymocytes of MRL-+/+ mice). Cell separation experiments using a cell sorter revealed that autologous killing was mediated for the most part by CD3int cells, while allogeneic killing was mediated entirely by natural killer (NK ) cells, TCRint cells and TCRhigh cells. Among CD3int cells, the NK1.1+ subset (i.e. NK1.1+ T cells) manifested a higher level of autologous killing than did the NK1.1− subset. Consistent with the results of a functional assay, it was found by reverse-transcription-polymerase chain reaction ( RT-PCR) assay that CD3int cells among liver MNC showed the expression of Fas ligand mRNA, while thymocytes expressed Fas mRNA. When class I major histocompatibility complex (MHC )− thymocytes (from b 2 -microglobulindeficient mice) were used as target cells, NK cells, but not CD3int cells, showed potent cytotoxicity. These results suggest that autologous killing is a major function of TCRint cells with self-reactivity, and that such killing is mediated by means of Fas ligand/Fas molecules.

Modulation of the endocrine and immune systems by well-controlled hyperthermia equipment

“…In addition to the increase in the total number of lymphocytes at the exposure time of hyperthermia, the number and proportion of CD56 + NK cells, CD57 + NK cells, and CD56 + (or CD57 + ) NKT cells were found to increase. It is known that these NK and NKT cells are associated with immune functions in animals and humans with malignancy (7,13,14,19). It is therefore speculated that the present phenomenon of the immune system might be important for the immunopotentiation of cancer patients.…”

Intensive expansion of natural killer T cells in the early phase of hepatocyte regeneration after partial hepatectomy in mice and its association with sympathetic nerve activation

“…However, such allogeneic cytotoxicity of liver lymphocytes isolated from mice with PHx was not significantly augmented. In a previous study, 22 we reported that selfreactive cytotoxicity of TCR int cells is mediated by the interaction of TCR on TCR int cells with MHC class I antigens (including CD1 antigen). To this end, we used both class I-deficient and class II-deficient thymocytes.…”

“…In contrast to NK cells, TCR int or CD3 int cells have unique cytotoxicity against syngeneic thymocytes (i.e., self-reactive cytotoxicity). 22 In this regard, we examined whether such self-reactive cytotoxicity of liver lymphocytes was suppressed at the early phase (0.5 day) of hepatocyte regeneration (Fig. 7).…”

“…Sympathetic nerve activation, possibly for the supply of oxygen and nutrients to proliferating hepatocytes, is always accompanied by hepatocyte regeneration. Because IL-2R␤ ϩ CD3 int cells can mediate self-reactive cytotoxicity, [21][22][23] it was also investigated how their cytotoxicity was modulated during hepatocyte regeneration. The biological significance of these cells at the time of hepatocyte regeneration is herein discussed in light of our findings.…”

Lung cancer with spontaneous regression of primary and metastatic sites: A case report

“…In the present case, however, spontaneous regression of the metastatic lesion was observed without any treatment of the primary or metastatic lesions; in addition, there was no infection of the primary or metastatic sites. It was recently reported that immunological mechanisms, including certain cytokines, such as interferon and tumor necrosis factor, may stimulate cytotoxic function against cancer cells, leading to spontaneous regression (17)(18)(19). Unfortunately, blood samples were not obtained for immunological evaluation, as there was no expectation of tumor regression at the time.…”