title: Increased Frequency of BK Virus-Specific Polyfunctional CD8+ T Cells Predict Successful Control of BK Viremia After Kidney Transplantation.
abstract: BK virus infection remains an important cause of loss of allograft function after kidney transplantation. We sought to determine whether polyfunctional T cells 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: 1 Division of Infectious Diseases, David Geffen School of Medicine at UCLA, Los Angeles, CA. 2 Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA. 3 Department of Biostatistics, UCLA School of Public Health, Los Angeles, CA. 4 Division of Nephrology, David Geffen School of Medicine at UCLA, Los Angeles, CA. 5 Department of Urology, David Geffen School of Medicine at UCLA, Los Angeles, CA.
authors.forename: Joanna M
authors.initials: JM
authors.lastname: Schaenman
authors.forename: Yael
authors.initials: Y
authors.lastname: Korin
authors.forename: Tiffany
authors.initials: T
authors.lastname: Sidwell
authors.forename: Fadi
authors.initials: F
authors.lastname: Kandarian
authors.forename: Nicholas
authors.initials: N
authors.lastname: Harre
authors.forename: David
authors.initials: D
authors.lastname: Gjertson
authors.forename: Erik L
authors.initials: EL
authors.lastname: Lum
authors.forename: Uttam
authors.initials: U
authors.lastname: Reddy
authors.forename: Edmund
authors.initials: E
authors.lastname: Huang
authors.forename: Phuong T
authors.initials: PT
authors.lastname: Pham
authors.forename: Suphamai
authors.initials: S
authors.lastname: Bunnapradist
authors.forename: Gabriel M
authors.initials: GM
authors.lastname: Danovitch
authors.forename: Jefferey
authors.initials: J
authors.lastname: Veale
authors.forename: H Albin
authors.initials: HA
authors.lastname: Gritsch
authors.forename: Elaine F
authors.initials: EF
authors.lastname: Reed
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use; D001739:BK Virus / Q000187:drug effects / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000821:virology; D016207:Cytokines / Q000276:immunology; D005260:Female; D006801:Humans; D016867:Immunocompromised Host; D007166:Immunosuppressive Agents / Q000009:adverse effects; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009894:Opportunistic Infections / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D010641:Phenotype; D027601:Polyomavirus Infections / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D011237:Predictive Value of Tests; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D014412:Tumor Virus Infections / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D014766:Viremia / Q000276:immunology / Q000821:virology
chemical_list: D000998:Antiviral Agents; D016207:Cytokines; D007166:Immunosuppressive Agents