| Project/Area Number |
11670235
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | TOKYO METROPOLITAN INSTITUTE OF GERONTOLOGY |
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Principal Investigator |
SHIMIZU Jun TOKYO METROPOLITAN INSTITUTE OF GERONTOLOGY, DEPARTMENT OF IMMUNOPATHOLOGY, RESEARCH SCIENTIST, 免疫病理部門, 研究員 (60291134)
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| Co-Investigator(Kenkyū-buntansha) |
SAKAGUCHI Shimon KYOTO UNIV.INSTITUTE FOR FRONTIER MEDICAL SCIENCES, DEPARTMENT OF EXPERIMENTAL PATHOLOGY, 再生医科学研究所, 教授 (30280770)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2000: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | CD25^+ T CELLS / TUMOR IMMUNOLOGY / ANERGY / アナージー |
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| Research Abstract |
We show that removal of a T cell subpopulation can evoke effective tumor immunity in otherwise non-responding animals. Elimination of CD25-expressing T cells, which constitute 5-10% of peripheral CD4^+ T cells in normal naive mice, elicited potent immune responses to syngeneic tumors in vivo and eradicated them. The responses were mediated by tumor-specific CD8^+ CTLs and tumor-nonspecific CD4^-8^- cytotoxic cells akin to NK cells. Furthermore, in vitro culture of CD25^+4^+ T cell-depleted splenic cell suspensions prepared from tumor-unsensitized normal mice led to spontaneous generation of similar CD4^-8^- cytotoxic cells capable of killing a broad spectrum of tumors ; reconstitution of CD25^+4^+ T cells inhibited the generation. In this culture, self-reactive CD25^-4^+ T cells responding to self peptides/class II MHC complexes on APCs spontaneously proliferated upon removal of CD^+4^+ T cells, secreting large amounts of IL-2. The IL-2 thus produced appeared to be responsible for the generation of CD4^-8^- NK cells as lymphokine-activated killer cells, because direct addition of an equivalent amount of IL-2 to the culture of CD4^-8^- cells generated similar lymphokine-activated killer/NK cells, whereas coculture of normal CD4^-8^- cells with CD25^-4^+ T cells from IL-2-deficient mice did not. Thus, removal of immunoregulatory CD25^+4^+ T cells can abrogate immunological unresponsiveness to syngenic tumors in vivo and in vitro, leading to spontaneous development of tumor-specific effector cells as well as tumor-nonspecific ones. This novel way of evoking tumor immunity would help to devise effective immunotherapy for cancer in humans.
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