Heterospecific Immunity Help to Sustain an Effective BK-virus Immune Response and Prevent BK-virus-associated Nephropathy

Abstract BK-virus-associated nephropathy (BKvAN) is a major complication in kidney transplant recipients, associated with a higher level of BK-virus (BKv) replication and leading to poor graft survival. In a large cohort of kidney transplant recipients with various BKv reactivation levels, we found that BKvAN was associated with a low BKv-specific memory CD8 T-cell functionality and an exhausted-like phenotype. This severe lymphocyte impairment was associated with a low level of class II HLA mismatches. In vitro experiments showed that allogeneic CD4 T cells partly restored BKv-specific memory CD8 T-cell responses. Our results suggest that in kidney transplant recipient, allogeneic CD4 T cells may provide a heterospecific help that maintain an effective BKv-specific memory CD8 T-cell response, and allows a better control of BKv replication in the kidney graft.