IMMUNOSUPPRESSION WITH ANTI-T CELL RECEPTOR V-BETA ANTIBODY IN LUNG TRANSPLANTATON

1998 Fiscal Year Final Research Report Summary

• Project/Area Number: 09671383
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Thoracic surgery
• Research Institution: The university of Tokushima
• Principal Investigator: SAKIYAMA Shoji The university of Tokushima, Medicine, assistant, 医学部, 助手 (60291986)
• Co-Investigator(Kenkyū-buntansha): TANIDA Nobuyuki The university of Tokushima, Medical School Hospital, assistant, 医学部附属病院, 助手 ; KONDO Kazuya The university of Tokushima, Medical School Hospital, assistant, 医学部附属病院, 助手 (10263815) ; MONDEN Yasumasa The university of Tokushima, Medicine, Professor, 医学部, 教授 (60028628)
• Project Period (FY): 1997 – 1998
• Keywords: lung transplantation / rat / TCR / TCR V-BETA / acute rejection / chronic rejection / immunosuppression

Research Abstract

We investigated the expression pattern of T cell receptor V-beta gene in graft infiltrating lymphocytes on the rat lung transplantation models. In the Brown Norway (BN, RT1) to Lewis (LEW, RT1) rat lung transplantation with no immunosuppresant, garafted lungs were acutely rejected within 7days after transplantation. Although lung allografts form BN to LEW were indefinitely accepted with a short course cyclosporine(CsA) administration after transplantation (on day 2 and 3 after transplantation , 25mg/kg, i.m.), late airway changes, such as granulation and submucosal fibrosis with infiltrating lymphocytes, were frequently observed in these lung allografts. These late airway changes were not observed in lung isografts treated with the same immunosuppressive treatment.
With these experimental models, TCR expression were evaluated in lung allografts to determine whether T cells infiltrating rejecting lung allografts employed restricted V-beta elements. Semi-quantitative PCR analysis of V-bet a gene usage was performed using V-beta specific primers.
The pattern of expression of V-beta gene in acutely rejecting lungs was different form that of isografted lungs. In acutely rejecting lungs, V-beta 5 and V-beta 8 gene were strongly expressed. In chronically rejecting lungs on day 30, V-beta 9 gene expression was stronger than that in lungs on day 30.
On day 30 after transplantation, the allografts treated with CsA showed perivascular and peribronchial cellular infiltration similar to that found on day 3 in the vascular phase of acute rejection. The peak of the number of the infiltrating cells in grafted lungs with CsA treated was shown on day 30 after transplantation, after that, the number of the infiltrating cells was gradualy reduced.
We postulated that allograft rejection is associated with restricted V-beta 5 and V-beta 8 TCR usage by graft infiltrating lymphocytes. Over expression of V-beta 9 TCR in allografted lungs on day 30 may related to suppressive mechanism for graft rejection.