Activation of anti-donor CD8 alloimmune response in clinically diagnosed acute rejection early after living-donor lobar lung transplantation and its impact on outcome

Abstract

Background

The characteristics and prognostic impacts of early graft infiltration after lung transplantation and clinically diagnosed acute rejection remain unclear. Furthermore, the alloimmune response status in lung transplantation remains uninvestigated.

Methods

In this retrospective cohort study, we evaluated 92 living-donor lobar lung transplantations (LDLLT) to establish the effect of graft infiltration—diagnosed as acute rejection—within one-month post-transplantation (cAR), on chronic lung allograft dysfunction (CLAD)-free LDLLT survival. The alloimmune response was evaluated using the carboxyfluorescein diacetate succinimidyl ester (CFSE)-mixed lymphocyte reaction (MLR) in lymphocytes isolated from donor and recipient blood one week after LDLLT. The anti-donor proliferation of CD4+ and CD8+ T cells was determined using flow cytometry.

Results

cAR was observed in 54 (58.7 %) patients who underwent LDLLT. The median postoperative day of cAR occurrence was 7 days (ranging between 5 and 28 days). Only one episode of cAR occurred in 51 patients (94.4 %). CLAD-free survival was significantly lower in patients who underwent cAR, especially within 2 years after LDLLT (p = 0.016). Thirteen CFSE-MLR assays were performed in seven consecutive LDLLT cases (six bilateral and one unilateral LDLLT). Increased anti-donor proliferation of CD8+ T cells, but not CD4+ T cells, was associated with cAR, irrespective of human leukocyte antigen (HLA) class I mismatch.

Conclusion

Early lung graft infiltration after LDLLT increases the risk of the early development of CALD. Augmented anti-donor CD8 + response was also associated with graft infiltration, which could not be predicted from HLA mismatches but could be monitored using MLR in LDLLT.