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Biomedical subjects

K Okuno

Publications and source records attributed to K Okuno.

At least 109 records · Page 6Linked to original sources
PubMed1984

Tolerance induction in tumor-specific effector T cells by presensitization with tumor antigens via the intragastric route.

The present study deals with the influence of presensitization with tumor antigens via the intragastric route on the development of syngeneic tumor-specific immunity. Tumor-specific T cell-mediated immunity could be induced in C3H/He mice by intradermal inoculation of syngeneic X5563 tumor cells, followed by the surgical resection of the tumor 7 days later (immunization procedure). However, when the mice were presensitized intragastrically (ig) with 10(8) X-irradiated (10,000 R) tumor cells for four consecutive days, these mice failed to show in vivo protective immunity even after the above immunization procedure. Winn assays performed with spleen cells from mice presensitized ig with X5563 tumor cells revealed that ig-induced suppression was specific for the tumor antigen used for the presensitization, and that suppressor cell activity was not detected in the induction or implementation of in vivo tumor-specific effector cell activity. It was also demonstrated that such unresponsiveness was accompanied by failure to develop delayed-type hypersensitivity and cytotoxic T cell responses to X5563 tumor antigens. These results are discussed in the light of the effect of presensitization with tumor antigens via inappropriate routes on the subsequent induction of in vivo tumor-specific immunity and in relation to the tumor escape mechanism which could occur in gastrointestinal cancers.

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PubMed1984

Interleukin-1 restores the impaired cytotoxic T lymphocyte generation in beige mutant mouse.

Spleen cells from C57BL/6 beige mouse showed significantly lower cytotoxic T lymphocyte (CTL) generation in vitro against allogeneic target cells as compared with spleen cells from the wild type, whereas the heterozygous littermate showed a response similar to that of the wild type. In contrast, the responsiveness of beige spleen cells in the mixed lymphocyte reaction against allogeneic stimulator cells was in the normal range, suggesting that beige spleen cells recognize allogeneic stimulator cells to the same extent as spleen cells from normal mouse, resulting in a significant proliferation. The addition of interleukin 1 (IL-1)-containing supernatant from lipopolysaccharide-stimulated J774.1 cells to the culture of spleen cells from beige mouse stimulated with allogeneic cells restored the impaired CTL generation in a dose-dependent manner. The molecules responsible for restoration of the impaired CTL response co-migrated with IL-1 on gel filtration. The addition of purified interleukin 2(IL-2) also augmented the induction of CTL from beige spleen cells. However, the magnitude of augmentation by IL-2 was appreciably lower than that of augmentation by IL-1. These results suggest that the role of IL-1 in the induction of CTL is not only to provide a signal for activated amplifier T cells to release IL-2, but also to magnify otherwise low responsiveness of CTL-precursors and/or CTL-helpers. Moreover, intraperitoneal injection of IL-1 without allo-antigenic stimulation was able to restore the in vitro CTL responsitivity to allo-antigen but not the natural killer cell activity, indicating that IL-1 has a therapeutic potential in vivo for preferentially correcting impaired CTL generation associated with beige mutation.

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PubMed1982

[Lymphokines].

Lymphokines are defined as nonimmunoglobulin secretory products of activated lymphocytes with a wide range of potent physiological effects on inflammation and immune responses. In this review, we summarized the recent development in lymphokine researches, including biochemical and immunological approaches. An increasing number of assay methods enabled us to detect various lymphokine activities released in the culture medium of lectin activated lymphoid cells. However, some of the results in a number of independent studies about lymphokines were rather complicated for precise interpretation, since the lymphoid cell-culture medium comprises a mixture of very heterogeneous lymphokines molecules. This problem has now been overcome by generating hybridomas producing rather homogeneous lymphokine. By utilizing such relatively homogeneous lymphokines, we analyzed the mechanism of cytoxic T lymphocyte (CTL) generation, and discussed a possibility for utilization of this approach to the future antitumor immunotherapy.

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