Narrowing of T-cell receptor beta variable repertoire during symptomatic herpesvirus infection in transplant patients.
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.
Wynn
Katherine K
KK
Australian Centre for Vaccine Development, and Tumour Immunology Laboratory, Department of Infectious Diseases, Queensland Institute of Medical Research, Brisbane, Queensland, Australia.
Crough
Tania
T
Campbell
Scott
S
McNeil
Keith
K
Galbraith
Andrew
A
Moss
Denis J
DJ
Silins
Sharon L
SL
Bell
Scott
S
Khanna
Rajiv
R
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
D000939:Epitopes; D016693:Receptors, Antigen, T-Cell, alpha-beta