title: Narrowing of T-cell receptor beta variable repertoire during symptomatic herpesvirus infection in transplant patients.
abstract: Primary infection or recrudescence of latent virus infection in transplant recipients can be manifested either as asymptomatic or symptomatic disease. Here we show that symptomatic human cytomegalovirus (HCMV) or Epstein-Barr virus (EBV) infection or recrudescence following solid organ transplantation (SOT) was coincident with a dramatic skewing of T-cell receptor beta variable (TRBV) repertoire, with expansions of monoclonal/oligoclonal clonotypes. As the clinical symptoms resolved, the peripheral blood repertoire reverted to a more diverse distribution. In contrast, SOT recipients with asymptomatic or no viral infection or recrudescence showed minimal or no skewing of the T-cell receptor repertoire to maintain peripheral blood repertoire diversity. More importantly, we show that large monoclonal/oligoclonal repertoire expansions are associated with the loss of HCMV-specific T-cell function observed in SOT patients undergoing symptomatic viral infection or recrudescence, whereas SOT recipients who maintain peripheral blood TRBV repertoire diversity and functional antigen-specific T-cell responses can resist clinical symptomatic disease in spite of high levels of viral load.
authors.affiliation: Australian Centre for Vaccine Development, and Tumour Immunology Laboratory, Department of Infectious Diseases, Queensland Institute of Medical Research, Brisbane, Queensland, Australia.
authors.forename: Katherine K
authors.initials: KK
authors.lastname: Wynn
authors.forename: Tania
authors.initials: T
authors.lastname: Crough
authors.forename: Scott
authors.initials: S
authors.lastname: Campbell
authors.forename: Keith
authors.initials: K
authors.lastname: McNeil
authors.forename: Andrew
authors.initials: A
authors.lastname: Galbraith
authors.forename: Denis J
authors.initials: DJ
authors.lastname: Moss
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Silins
authors.forename: Scott
authors.initials: S
authors.lastname: Bell
authors.forename: Rajiv
authors.initials: R
authors.lastname: Khanna
mesh_terms: D000328:Adult; D000368:Aged; D049109:Cell Proliferation; D000939:Epitopes / Q000276:immunology; D006566:Herpesviridae Infections / Q000276:immunology* / Q000821:virology*; D006801:Humans; D008875:Middle Aged; D016377:Organ Transplantation; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D012008:Recurrence; D013601:T-Lymphocytes / Q000166:cytology / Q000821:virology; D019562:Viral Load
chemical_list: D000939:Epitopes; D016693:Receptors, Antigen, T-Cell, alpha-beta