T‐Cell Clonal Change after Allo‐Kidney Transplantation in Humans

Abstract

Whether T cells circulating peripherally express changes at a clonal level after renal transplantation is uncertain. To clarify this issue, we analyzed T-cell clonality of peripheral blood lymphocytes (PBLs) in 12 renal transplant recipients by a novel polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) method that can discriminate T-cell clones with different T-cell receptor (TCR) Vb motifs. The PCR-SSCP study showed that after transplantation, only a few distinct T-cell clonotypes accumulated in the absence of clinical episodes, irrespective of the compatibility of HLA antigens. In contrast, various T-cell clones appeared in cases of acute rejection (AR) and infection. These subsided immediately after the AR was resolved; however, they remained long after the resolution of the infection. In a case of AR followed by an infectious episode, distinct T-cell clones appeared concomitantly with each episode. Several of them disappeared or remained thereafter. In one case, significant numbers of accumulating bands were observed by in-vitro stimulation by mixed lymphocyte reaction (MLR); several were identical to those found in vivo. However, some of those that did not appear in vitro were apparent in vivo. In conclusion, the appearance of Tcell clonotypes at a peripheral level indicates the existence of immunologically activated T-cell clones, which were significantly affected by immunosuppressive therapy. It was also determined that the T-cell immune system is much more complicated in vivo than in vitro.

Mixed Lymphocyte Cultures Can Predict TCR Vβ Repertoires of T Cells Infiltrating Kidney Transplants during Acute Rejection Episodes

“…Some similarities but also some differences in predominant V␤ gene usage were noted between GIL and MLC populations (20).…”

Evaluation of T-Cell Receptor Repertoires in Patients with Long-Term Renal Allograft Survival

“…Owens et al (25) suggested that the establishment of short-term stable renal allograft function (1 year posttransplantation) requires the deletion of certain T cells from peripheral blood. Whereas many studies described TCR usage during graft rejection in humans (14,(26)(27)(28)(29), to our knowledge, no studies on TCR usage in long-term functioning kidney transplants have hitherto been reported.…”

Skew in T-cell receptor usage and clonal T-cell expansion in patients with chronic rejection of transplanted kidneys

“…Clonality of T cells has been analyzed by Southern blot hybridization (27), CDR3 length analysis (15), and single-strand conformation polymorphism (28). We analyzed TCR repertoires in a quantitative fashion and clonal T-cell expansion in the TCRBV segments in the present study.…”

“…Hagihara et al demonstrated that clonal expansion of T cells occurred in peripheral blood at an early period after kidney transplantation using the PCR single-strand conformation polymorphism method (28). They reported that various T-cell clones appeared in the recipients with an acute rejection of the transplanted kidney and a viral infection.…”