The Balance of CD8-Positive T Cells and PD-L1 Expression in the Myocardium Predicts Prognosis in Lymphocytic Fulminant Myocarditis

Abstract

<b><i>Introduction:</i></b> The clinical significance and prognostic value of T cell involvement and programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) have not been established in lymphocytic fulminant myocarditis (FM). We investigated the prognostic impact of the number of CD4⁺, CD8⁺, FoxP3⁺, and PD-1⁺ T cells, as well as PD-L1 expression, in cardiomyocytes in lymphocytic FM. <b><i>Methods:</i></b> This is a single-center observational cohort study. Myocardial tissue was obtained from 16 consecutive patients at lymphocytic FM onset. The median follow-up was 140 days. Cardiac events were defined as a composite of cardiac death and left ventricular-assist device implantation. CD4, CD8, FoxP3, PD-1, and PD-L1 immunostaining were performed on myocardial specimens. <b><i>Results:</i></b> The median age of the patients was 52 years (seven men and nine women). There was no significant difference in the number of CD4⁺ cells. The number of CD8⁺ cells and the CD8⁺/CD4⁺ T cell ratio were higher in the cardiac event group (Event+) than in the group without cardiac events (Event−) (<i>p</i> = 0.048 and <i>p</i> = 0.022, respectively). The number of FoxP3⁺ T cells was higher in the Event+ group (<i>p</i> = 0.049). Although there was no difference in the number of PD-1⁺ cells, cardiomyocyte PD-L1 expression was higher in the Event+ group (<i>p</i> = 0.112). Event-free survival was worse in the group with a high CD8⁺ cell count (<i>p</i> = 0.012) and high PD-L1 expression (<i>p</i> = 0.049). When divided into three groups based on the number of CD8⁺ cells and PD-L1 expression (CD8^highPD-L1^high [<i>n</i> = 8], CD8^lowPD-L1^high [<i>n</i> = 1], and CD8^lowPD-L1^low [<i>n</i> = 7]), the CD8^highPD-L1^high group demonstrated the worst event-free survival, while the CD8^lowPD-L1^high group had a favorable prognosis without cardiac events (<i>p</i> = 0.041). <b><i>Conclusion:</i></b> High myocardial expression of CD8⁺ T cells and PD-L1 may predict a poor prognosis in lymphocytic FM.