Research Abstract |
In order to characterize the T-cell population participating in renal allograft rejection, I performed several analyses using biopsy specimens. The following results were obtained : 1) For the accurate analysis of the T-cell receptor (TCR) diversity using biopsy specimens, I developed a non-radioisotopic micromethod, in which TCR cDNAs amplified by an anchored polymerase chain reaction were hybridized with an array of TCR variable gene DNA fixed on a nylon membrane. 2) TCR analysis allowed me to assess the clonality of T-cells participating in renal allograft rejection. The method was particularly useful to monitor the change in clonality after immunosuppressive treatment for the rejection. 3) The degree of clonality in renal infiltrating T-cell was not significantly different between acute rejection (AR) ard chronic rejection (CR). However, difference in clonality between infiltrating cells ard that in peripheral blood was larger in AR than CR, indicating that particular T-cel 1 clones accumulated in the allografts receiving AR. 4) Virally infected allograft often showed T-cell clonality similar to that of rejected allograft and it was difficult to discriminate them only by clonality analysis. 5) The degree of infiltration of alpha-beta T cells, CD4-positive T cells, and CD8-positive T cells in CR allografts were not different from that in AR allografts, indicating that CR, as AR, was mediated by these immune cells. 6) The frequency of detection of interferon-gammas in allografts was not significantly different between CR and AR, indicating that Th1 cells participated in both CR and AR. 7) Interleukin-4 was detected only in one-third of CR allografts and not in AR allografts, suggesting that some CR were mediated by Th2 cells.
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