1989 Fiscal Year Final Research Report Summary
A basic study on immunotherapy of autoimmune male infertility with antigen-specific suppressor T cell factor (TsF)
| Project/Area Number |
62570728
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Urology
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| Research Institution | Kagawa Medical School |
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Principal Investigator |
HOJO Kenji Kagawa Medical School, School of Medicine, Professor, 医学部, 教授 (90046863)
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| Co-Investigator(Kenkyū-buntansha) |
HIRAMINE Chiharu Kagawa Medical School, School of Medicine, Research Associate, 医学部, 助手 (30047203)
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| Project Period (FY) |
1987 – 1989
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| Keywords | Therapy for infertility / Suppressor T cell line / Suppressor T cell factor / Effector T cell line / Experimental autoimmune orchitis / Antisperm immunity |
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| Research Abstract |
Experimental autoimmune orchitis (EAO) has proved to be a useful model for investigating the immunopathogenesis of male infertility and immunoregulatory mechanisms of this disease.
There has been little or no evidence of effective therapy for autoimmune male infertility. Past ten years, our studies on the immunoregulation in guinea pig EAO have demonstrated the generation of suppressor T cells or their factors responsible for suppressing EAO induction and interfering with local adoptive transfer of EAO using antigen-specific effector T cells. Treatment of murine EAO with suppressor T cell factor (TsF) offers an especially attractive model to develop and validate a novel and specific immunotherapy for autoimmune male infertility. Results obtained from our project during the past 3 years are as follows:
1. Suppressor T cells (Lyt-2^+) capable of inhibiting the EAO induction were induced in C3H/He mice by five doses of soluble (aggregate-free) testicular antigen intravenously.
2. A suppresso
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r T cell line was derived through in vitro cultivation of spleen cells from C3H/He mice that were rendered hyperimmune by repeated subcutaneous injections with syngeneic testicular cells. This lined cells had the L3T4^+ phenotype and the capability of suppressing on-going EAO.
3. Murine EAO with very high incidence could be developed in C3H/He mice by administering two or three subcutaneous injections of syngeneic testicular germ cells (TC) alone without resorting to adjuvant or cyclophosphamide. This model provides a very useful method for estimation of EAO-suppressing activity of TsF.
4. An effector T cell line (L3T4^+) having the capability of transferring EAO systematically into naive recipients was established in BALB/c mice. This cell line is valuable for study on immunoregulation at the effector stage of EAO.
5. Accurate and reproducible ELISA assay for detecting autoantibodies against sperm or TC in mice was developed.
Thus, although the results from the present studies from our laboratory do not as yet isolate TsF molecules secreted or extracted from monocloned suppressor T cells or suppressor T cell hybridomas, preparations for investigating the TsF (e.g. TsF-secreting cells and assay systems for TsF activity) are making smooth progress. The isolation of a cDNA clone that may specify a polypeptide chain for the suppressor function is an attractive and obligatory subject. Less
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