CD4+ T Cell Immune Response to VP1 and VP3 in BK Virus Infected Recipients of Renal Transplantation.

OBJECTIVE: To investigate the characteristics of BK virus (BKV) specific cellular immune response in the recipients who have early infection with BKV after renal transplantation.

METHODS: The recipients of renal allografts (n = 30) were divided into groups of BK virus nephropathy (BKVN), viruria, and viremia. The BKV load was observed with real-time fluorescence quantitative polymerase chain reaction in urine and blood every three months. The values of serum creatinine (SCr) were detected. The peripheral blood mononuclear cells (PBMCs) were cultivated with overlapping peptide pool containing BKV structural proteins VP1, VP2, and VP3, and regulatory proteins large tumor antigen (LT-Ag) and small tumor antigen (st-Ag), to stimulate in vitro specific cellular immunoresponse. Flow cytometry was used to measure the proliferation of CD3+/CD4+/CD8+ T and interferon [INF]-γ/interleukin [IL]-2/tumor necrosis factor [TNF]-α T cell subsets.

RESULTS: The BKV infection increased SCr values in recipients of renal transplantation. CD4+ T cells were dominant (>90%) in the in vitro cellular immunoresponse to VP1, VP2, VP3, LT-Ag, and st-Ag. At the presence of viremia and BKVN, IL-2/IFN-γ+/TNF-α+ CD4+ T cells showed significantly decreased in vitro cellular immunoresponse to VP1, VP2, and VP3 (p < 0.05), but insignificantly changed to LT-Ag and st-Ag (p > 0.05). For the cases of viruria and viremia, IL-2/IFN-γ+/TNF-α+ CD4+ T cells showed significantly higher in vitro cellular immunoresponse to VP1, VP2, and VP3 than to LT-Ag and st-Ag (p < 0.05). The immunogenicity of VP1 and VP3 was significantly higher than that of VP2 (p < 0.05).

CONCLUSIONS: The BKV infection increases SCr values, and CD4+ T cells are dominant in the in vitro BKV specific cellular immunoresponse in the recipients of renal transplantation. Viremia significantly decreased the immunoresponse to VP1, VP2, and VP3. There is the significantly stronger immunoresponse to VP1 and VP3 when compared with that to VP2, LT-Ag, and st-Ag, suggesting that VP1 and VP3 may be the major targets for the BKV specific immune response.