Sara van den Berg

185 7 Duration of CMV infection Figure 3. CMV-induced changes in the CD8+ T-cell pool are established early after CMV infection. A . Absolute numbers of CD8+ T-cell subsets compared between CMV-, ST CMV+ and LT CMV+ individuals indi- cated by boxplots. B . Relationship of duration of CMV infection with CD8+ T EMRA cells numbers. C . CD8+ T EMRA cells numbers at endpoint in individuals that seroconverted at younger age (≤38yr of age) compared to those individuals who converted at older age (≥45yr of age, mean age 58.5±8.1). D-G. CMV-specific T-cells in HLA-A2 positive individuals for pp65-epitope NLVPMVATV are compared between ST CMV+ and LT CMV+ individuals in numbers of cells ( D ), percentage of total CD8 ( E ), percentage of T EMRA cells ( F ) and expression of senescence marker KLRG-1 ( G ). H. IFN γ production of CD8+ T-cells after CMV-specific peptide stimulation in CMV-, ST CMV+ and LT CMV+ individuals (n=27) I. Percentage of CD8+ T-cells responding polyfunctionally to CMV with production of IFN γ , TNFa, MIP-1 β and/orCD107 in ST CMV+ and LT CMV+ individuals. *=P<0.05 ****P<0.0001. Boxplots show median with interquartile range. Colors of symbols represent CMV-serostatus. Green: CMV-, blue: ST CMV+, purple: LT CMV+. Changes in the CD4+ T-cell pool are established early after CMV infection, and are most pronounced in older CMV-seroconverters Next, we studied the impact of duration of CMV infection on the CD4+ T-cell pool by comparing CD4+ T-cells at end point between ST CMV+ individuals and LT CMV+ individuals. CMV seropositivity was associated with higher numbers of T EM and T EMRA CD4+ T-cells ( Figure 4A ), which was mainly due to the presence of relatively high numbers of intermediate and late-stage differentiated T EM and T EMRA cells (data not shown).