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.