2000 Fiscal Year Final Research Report Summary
MONITORING OF T-CELL RESEPTOR COMPLEMENTARITY-DETERMINIG REGION 3(CDR3)DIVERSITY AFTER HUMAN ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION
| Project/Area Number |
10670932
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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 |
Hematology
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| Research Institution | AKITA UNIVERSITY SCHOOL OF MEDICINE |
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Principal Investigator |
HIROKAWA Makoto AKITA UNIVERSITY SCHOOL OF MEDICINE, THIRD DEPARTMENT OF INTERNAL MEDICINE, LECTURER, 医学部, 助手 (50241667)
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| Co-Investigator(Kenkyū-buntansha) |
KAWABATA Yoshinari AKITA UNIVERSITY SCHOOL OF MEDICINE, THIRD DEPARTMENT OF INTERNAL MEDICINE, CRINICAL FELLOW, 医学部, 医員(臨床)
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| Project Period (FY) |
1998 – 2000
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| Keywords | T-cell receptor / repertoire / hematopoietic stem cell transplantation / CDR3 / peripheral expansion / T-cell regeneration / immunodeficiency / clone |
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| Research Abstract |
We investigated the reconstitution of T-cell receptor repertoire after human allogeneic hematopoietic stem cell transplantation. We found that skewed repertoires of the T-cell receptor-β chain variable region(TCRBV)and the TCR-α chain variable region(TCRAV)were observed at an early period after transplantation and that normalization of skewed repertoires required several years in adults. The magnitude of skewing in the usage of TCRBV and AV was small in pediatric patients and normalization of skewed repertoires was faster in children than in adults. Extensive clonal expansion of T lymphocytes caused post-transplant skewing of TCR repertoires and clonally expanded T lymphocytes were enriched in the CD8+CD28- fraction. CDR3 size spectratyping analysis for the TCR-β and -δ chains revealed that immunocompetence in recipients was associated with the reconstitution of repertoire diversity of TCRαβ+, but notTCRγδ+, T lymphocytes. These results suggest that peripheral T-cell expansion may be the principal mechanism of T-cell regeneration after hematopoietic stem cell transplantation.
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