1989 Fiscal Year Final Research Report Summary
Morphology and function of lymphocytes expanded in granular lymphocyte leukemia
| Project/Area Number |
63480280
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Hematology
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| Research Institution | Tokyo Women's Medical College |
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Principal Investigator |
OSHIMI Kazuo Tokyo Women's Med.Coll. Fac. Med. Associate Prof., 医学部, 助教授 (40089991)
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| Co-Investigator(Kenkyū-buntansha) |
YAMADA Osamu Tokyo Women's Med.Coll. Fac. Med. Assistant, 医学部, 助手 (30167712)
AKAHOSHI Masako Tokyo Women's Med.Coll. Fac. Med. Assistant, 医学部, 助手 (40150974)
TAKAHASHI Masatomo Tokyo Women's Med.Coll. Fac. Med. Assistant, 医学部, 助手 (90119991)
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| Project Period (FY) |
1988 – 1989
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| Keywords | Granular lymphocyte leukemia / Granular lymphocyte proliferative disorders / non-MHC-restricted cytotoxicity / gammadelta T cells / Interleukin 2 receptor |
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| Research Abstract |
(1) Immunological characteristics of granular lymphocytes (GL).
Lymphocytes expanded in the peripheral blood in patients with granular lymphocyte proliferative disorders (GLPD) are divided into CD3+ T-cell type and CD3-16+ NK-cell type. The incidence of T- GLPD is 64%, the number being lower than western countries. GL in T-GLPD usually lack non-MHC- restricted cytotoxicity and possess ADCC, whereas those in NK-GLPD possess both non-MHC-restricted and ADCC cytotoxicity. ADCC of T-GLPD is inhibited by the addition of anti-CD3 and anti-CD8 monoclonal antibodies (mAb), suggesting that CD3 and CD8 antigens regulate ADCC in T-GLPD. GL express IL-2 receptor (R)beta chain al one , and the proliferation of GL is mediated thorough this R in autocrine and paracrine fashion. Anti-IL-2Pbeta mAb inhibits GL proliferation.
(2) Ultrastructure of GL
When gamma delta-TCR-positive GL and K562 target cells are mixed, the GL enter into K562 cells. This phenomenon is called emperipolesis. Emperipolesis is not found in alpha beta-TCR-positive T cells or NK cells. Further characterization of emperipolesis is under investigation using gamma delta- T-cell clones.
(3) Colony assay
GL obtained from patients with GLPD and pure red-cell aplasia (PRCA) inhibit normal donor-derived CFU-E colonies, and the supernatants of GL also inhibit the colony formation. Since anti-interferon gamma- antibody added in the CFU-E culture system abrogates the GL-mediated CFU-E inhibition, it is likely IFN-gamma and/or related substance may be responsible for the inhibition.
(4) Analysis of TCR genes
Most patients with T-GLPD exhibit monoclonal rearrangements of TCR-beta and gamma genes, whereas those with NK-GLPD remain in germ-line configuration.
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