title: Cross-reactive anti-viral T cells increase prior to an episode of viral reactivation post human lung transplantation.
abstract: 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.
authors: Department of Medicine, Monash University, Central Clinical School, The Alfred Centre, Melbourne, Victoria, Australia.
authors: Thi H O
authors: TH
authors: Nguyen
authors: Glen P
authors: GP
authors: Westall
authors: Tara E
authors: TE
authors: Bull
authors: Aislin C
authors: AC
authors: Meehan
authors: Nicole A
authors: NA
authors: Mifsud
authors: Tom C
authors: TC
authors: Kotsimbos
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D016022:Case-Control Studies; D003429:Cross Reactions / Q000276:immunology*; D003587:Cytomegalovirus / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000276:immunology; D006085:Graft Survival / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D016040:Lung Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D014184:Transplantation, Homologous; D014775:Virus Activation / Q000276:immunology*
chemical_list: D000998:Antiviral Agents; D006680:HLA Antigens