Background Deficiencies in CMV-specific T cell immunity pre-transplant increase patient risk of CMV reactivation and disease post-transplantation. The aim of this study was to investigate and compare CMV-specific cellular immunity in healthy virus carriers and lung transplant candidates pre-transplant to identify key immune mediators associated with functional defects in CMV-specific T cells. Methods A prospective cohort study of 43 adult lung transplant candidates and 14 healthy virus carriers was conducted in Brisbane, Australia. Intracellular cytokine staining and immune phenotyping (by multiparametric flow cytometry) were performed to explore phenotypic and functional characteristics of CMV-specific T cells. Results In this study, 60% of lung transplant candidates were CMV-seropositive pre-transplant. The numbers of CMV-specific T cells in the periphery were comparable between CMV-seropositive lung transplant candidates and healthy virus carriers. Effector molecule (CD107a, IFN-γ, TNF-α, and IL-2) expression on CMV-specific CD8+ and CD4+ T cells was significantly higher in CMV-seropositive lung transplant candidates compared to healthy virus carriers. However, expression of key T cell function mediators (CD11a, CD29, CD49f, and Granzyme B) was significantly higher in CMV-seropositive lung transplant candidates compared to healthy virus carriers. Conversely, expression levels of CD49d, CD103, and Eomes on T cells and CMV-specific T cells were significantly lower in CMV-seropositive lung transplant candidates compared to healthy virus carriers. Conclusions The findings from this study reveal significant phenotypic differences between healthy virus carriers and lung transplant candidates. Assessment of pre-existing CMV-specific T-cell immunity in lung transplant candidates may help to inform and personalise post-transplant clinical management.

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Altaf M

Papers

Phenotypic and functional characterisation of circulating cytomegalovirus-specific T cells in healthy virus carriers and lung transplant candidates