Latent Cytomegalovirus infection amplifies CD8 T-lymphocyte mobilisation and egress in response to exercise

Exercise induces mobilisation of CD8+ T lymphocytes (CD8TL) into the peripheral blood. This response is largely confined to effector-memory CD8TLs: antigen experienced cells which have a strong tissue-homing and effector potential. This study investigated whether effector-memory cells also account for the CD8TL egress from peripheral blood following exercise. As latent Cytomegalovirus (CMV) infection is associated with a robust expansion in the number and proportion of effector-memory CD8TLs, we also investigated if CMV serostatus was a determinant of the CD8TL responses to exercise.Fourteen males (Mean age 35, SD ± 14 yrs), half of whom were CMV seropositive (CMV+), ran on a treadmill for 60 min at 80% V˙O2 max. Blood was collected at baseline, during the final minute of exercise, and 15 min and 60 min thereafter. CD8TL memory subsets were characterised by flow cytometry, using the cell-surface markers CD45RA, CD27, and CD28.The results confirmed that CD8TLs with an effector-memory phenotype (CD27−CD28−CD45RA+/−) exhibited the largest increase during exercise (+200% to +250%), and also showed the largest egress from blood 60 min post-exercise (down to 40% of baseline values). Strikingly, the mobilisation and subsequent egress of total CD8TLs was nearly twice as large in CMV+ individuals. This effect appeared specific to CD8TLs, and was not seen for CD4+ T lymphocytes or total lymphocytes. This effect of CMV serostatus was largely driven by the higher numbers of exercise-responsive effector-memory CD8TLs in the CMV+ participants.This is the first study to demonstrate that infection history is a determinant of immune system responses to exercise.

Research highlights
► Differentiated effector-memory cells are selectively mobilised during exercise.
► The same highly cytotoxic memory cells egress from peripheral blood post-exercise.
► Cytomegalovirus seropositivity exercise-induced CD8+T lymphocyte mobilisation.