Cross-Reactive Anti-Viral T Cells Increase Prior to an Episode of Viral Reactivation Post Human Lung Transplantation
AuthorNguyen, THO; Westall, GP; Bull, TE; Meehan, AC; Mifsud, NA; Kotsimbos, TC
Source TitlePLoS One
PublisherPUBLIC LIBRARY SCIENCE
University of Melbourne Author/sNguyen, Thi Hoang Oanh
AffiliationMicrobiology and Immunology
Document TypeJournal Article
CitationsNguyen, T. H. O., Westall, G. P., Bull, T. E., Meehan, A. C., Mifsud, N. A. & Kotsimbos, T. C. (2013). Cross-Reactive Anti-Viral T Cells Increase Prior to an Episode of Viral Reactivation Post Human Lung Transplantation. PLOS ONE, 8 (2), https://doi.org/10.1371/journal.pone.0056042.
Access StatusOpen Access
Human Cytomegalovirus (CMV) reactivation continues to influence lung transplant outcomes. Cross-reactivity of anti-viral memory T cells against donor human leukocyte antigens (HLA) may be a contributing factor. We identified cross-reactive HLA-A*02:01-restricted CMV-specific cytotoxic T lymphocytes (CTL) co-recognizing the NLVPMVATV (NLV) epitope and HLA-B27. NLV-specific CD8+ T cells were expanded for 13 days from 14 HLA-A*02:01/CMV seropositive healthy donors and 11 lung transplant recipients (LTR) then assessed for the production of IFN-γ and CD107a expression in response to 19 cell lines expressing either single HLA-A or -B class I molecules. In one healthy individual, we observed functional and proliferative cross-reactivity in response to B*27:05 alloantigen, representing approximately 5% of the NLV-specific CTL population. Similar patterns were also observed in one LTR receiving a B27 allograft, revealing that the cross-reactive NLV-specific CTL gradually increased (days 13-193 post-transplant) before a CMV reactivation event (day 270) and reduced to basal levels following viral clearance (day 909). Lung function remained stable with no acute rejection episodes being reported up to 3 years post-transplant. Individualized immunological monitoring of cross-reactive anti-viral T cells will provide further insights into their effects on the allograft and an opportunity to predict sub-clinical CMV reactivation events and immunopathological complications.
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