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Transplantation. 2011 Dec 15;92(11):1269-77. doi: 10.1097/TP.0b013e318234e0e5.

Novel approach for improved assessment of phenotypic and functional characteristics of BKV-specific T-cell immunity.

Author information

1
Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité University Medicine Berlin, Campus Virchow Clinic, Berlin, Germany.

Abstract

BACKGROUND:

BKV-associated nephropathy represents a serious complication of the posttransplant period in kidney transplant recipients. Monitoring BKV-specific immunity is of a special importance for estimation of clinical course in patients with BKV reactivation. Our recent data demonstrated that all five BKV antigens are immunogenic and elicit T-cell responses varying within patients. Therefore, all five BKV proteins should be evaluated for the assessment of BKV-specific immunity. However, analysis of five proteins performed separately is time- and cost-intensive and requires large amount of blood.

METHODS:

Using novel approach of a mixture of overlapping peptide pools encompassing all five BKV antigens (viral protein [VP] 1, VP2, VP3, large tumor antigen, and small tumor antigen) and multiparameter flow cytometry, we evaluate BKV-specific T cells in patients with a previous/present severe long-lasting or transient BKV reactivation. Patients without BKV reactivation were used as control.

RESULTS:

In this study, we show that using mixture of overlapping peptide pool results in the magnitude of CD4- and CD8-positive BKV-specific T-cell response, which is significantly higher compared with any frequencies detected by previously used single BKV antigen stimulation. Of interest, patients with a history of rapid BKV clearance had significantly higher frequency of multifunctional interferon gamma-γ/interleukin (IL)-2/tumor necrosis factor-α and IL-2/tumor necrosis factor-α CD4-positive T cells, suggesting protective potential of polyfunctional T cells. Furthermore, we did not find IL-17-producing BKV-specific memory T cells in patients recovered from BKV reactivation.

CONCLUSIONS:

Here, we established a fast and sensitive approach allowing the most comprehensive assessment of the total BKV immunity performed to date and offer a new platform for further prospective studies.

PMID:
22124284
DOI:
10.1097/TP.0b013e318234e0e5
[Indexed for MEDLINE]

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