Narrowing of T-cell receptor beta variable repertoire during symptomatic herpesvirus infection in transplant patients

作者:Wynn Katherine K; Crough Tania; Campbell Scott; McNeil Keith; Galbraith Andrew; Moss Denis J; Silins Sharon L; Bell Scott; Khanna Rajiv*
来源:Immunology and Cell Biology, 2010, 88(2): 125-135.
DOI:10.1038/icb.2009.74

摘要

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. Immunology and Cell Biology (2010) 88, 125-135; doi:10.1038/icb.2009.74; published online 6 October 2009