TY - JOUR
T1 - Increased frequency of BK virus-specific polyfunctional CD8+ T cells predict successful control of BK viremia after kidney transplantation
AU - Schaenman, Joanna M.
AU - Korin, Yael
AU - Sidwell, Tiffany
AU - Kandarian, Fadi
AU - Harre, Nicholas
AU - Gjertson, David
AU - Lum, Erik L.
AU - Reddy, Uttam
AU - Huang, Edmund
AU - Pham, Phuong T.
AU - Bunnapradist, Suphamai
AU - Danovitch, Gabriel M.
AU - Veale, Jefferey
AU - Albin Gritsch, H.
AU - Reed, Elaine F.
N1 - Funding Information:
This work was funded in part by NIH Clinical and Translational Science Institute grant UL1TR000124.
Publisher Copyright:
© 2017 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2017/6
Y1 - 2017/6
N2 - Background. BK virus infection remains an important cause of loss of allograft function after kidney transplantation.We sought to determine whether polyfunctional Tcells secreting multiple cytokines simultaneously, which have been shown to be associated with viral control, could be detected early after start of BK viremia, which would provide insight into the mechanism of successful antiviral control. Methods. Peripheral blood mononuclear cells collected during episodes of BK viral replication were evaluated by multiparameter flow cytometry after stimulation by overlapping peptide pools of BK virus antigen to determine frequency of CD8+ and CD4+ T cells expressing 1 or more cytokines simultaneously, as well as markers of T-cell activation, exhaustion, and maturation. Results. BK virus controllers, defined as those with episodes of BK viremia of 3 months or less, had an 11-fold increase in frequency of CD8+ polyfunctional T cells expressing multiple cytokines, as compared with patients with prolonged episodes of BK viremia. Patients with only low level BK viremia expressed low frequencies of polyfunctional T cells. Polyfunctional T cells were predominantly of the effector memory maturation subtype and expressed the cytotoxicity marker CD107a. Conclusions. Noninvasive techniques for immune assessment of peripheral blood can provide insight into the mechanism of control of BK virus replication and may allow for future patient risk stratification and customization of immune suppression at the onset of BK viremia.
AB - Background. BK virus infection remains an important cause of loss of allograft function after kidney transplantation.We sought to determine whether polyfunctional Tcells secreting multiple cytokines simultaneously, which have been shown to be associated with viral control, could be detected early after start of BK viremia, which would provide insight into the mechanism of successful antiviral control. Methods. Peripheral blood mononuclear cells collected during episodes of BK viral replication were evaluated by multiparameter flow cytometry after stimulation by overlapping peptide pools of BK virus antigen to determine frequency of CD8+ and CD4+ T cells expressing 1 or more cytokines simultaneously, as well as markers of T-cell activation, exhaustion, and maturation. Results. BK virus controllers, defined as those with episodes of BK viremia of 3 months or less, had an 11-fold increase in frequency of CD8+ polyfunctional T cells expressing multiple cytokines, as compared with patients with prolonged episodes of BK viremia. Patients with only low level BK viremia expressed low frequencies of polyfunctional T cells. Polyfunctional T cells were predominantly of the effector memory maturation subtype and expressed the cytotoxicity marker CD107a. Conclusions. Noninvasive techniques for immune assessment of peripheral blood can provide insight into the mechanism of control of BK virus replication and may allow for future patient risk stratification and customization of immune suppression at the onset of BK viremia.
UR - http://www.scopus.com/inward/record.url?scp=84978036131&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84978036131&partnerID=8YFLogxK
U2 - 10.1097/TP.0000000000001314
DO - 10.1097/TP.0000000000001314
M3 - Article
C2 - 27391197
AN - SCOPUS:84978036131
SN - 0041-1337
VL - 101
SP - 1479
EP - 1487
JO - Transplantation
JF - Transplantation
IS - 6
ER -