PROPAGATION OF A UNIQUE V^σ1-BEARING V^σT CELLS CLONE WITHIN GRAFT INFILTRATES OF HUMAN LIVER TRANSPLANTATION TOLERANCE-IMMUNOPRIVILEGED LIVER SPECIFIC ?-

点击翻译按钮获取中文摘要

We reported that V^σ1bearing Y^σT cells (V^σ1 cells), which represent a minor subset of Y^σT cells in normal individuals, predominate over V^σ 2bearing Y^σT cells (V^σ2 cells) in peripheral blood of tolerant patients after liver transplantation (LTx). We further examined LTx tolerant patients for V^σ1 cells/V^σ2 cells (V^σ1/V^σ2) ratio and sequence in V^σ1 TCR chains in graft infiltrates. To elucidate whether V^σ1 cells are responsible for immunoprivilege of LTx, highly immunogenic intestinal Tx (ITx) was studied in addition. Method Protocol biopsy was performed in patients whose grafts were functioning well despite the absence of or minimum immunosuppression after LTx (N= 18) and intestinal Tx (ITx) (N=3)(Gr-To1). Total RNA was extracted to synthesize cDNA. V^σ1 and V^σ2 gene expressions were quantified by real-time PCR, and CDR3 sequence in V^σ1 TCR chains was analyzed. The results were compared to those of chronically rejecting grafts (Gr-CR N=9) and normal liver (Gr-Nor N=6) in LTx and native intestines of the patients (Gr-Nat N=2) in ITx. Results LTx ; V^σ1/V^σ2 ratio was the highest in Gr-Tol, compared to those in Gr-CR and Gr-Nor (p<0.05). Sequences of V^σ1 in Gr-Tol were shifted towards mono-/oligo-clonal pattern, while polyclonal in Gr-CR. One dominant sequence was observed in 8 out of 9 tolerant patients but identical sequence was not seen in Gr-CR. ITx ; Unlike LTx, there was no difference between V^σ1/V^σ2 ratio of Gr-Tol and Gr-Nat. Neither mono-/oligo-clonal shift of V^σ1 sequence nor any common sequence was observed among patients in Gr-Tol. Conclusion A unique V^σ1T cell clone propagated within tolerant liver graft but not tolerant intestinal graft. We hypothesize that this propagation is liver-antigen-selected and associated with a mechanism of immunoprivilege of liver Tx.