Development of cytomegalovirus and adenovirus-specific memory CD4 T-cell functions from birth to adulthood

Age-related changes in memory CD4 T cells (CD4) are poorly known. To address this issue, CD4 proliferative and cytokine responses to an anti-CD3 monoclonal (CD3), to cytomegalovirus (CMV), and to adenovirus (AdV) were assessed in 57 children (age, 0.07-17.16 y) and 17 adults. Results showed i) accumulation of memory CD4 with aging, with 2-3 times more central-memory T cell (TCM; CD45RA/CD62L) than effector-memory T cell (TEM; CD45RA/62L) CD4 at any age. ii) In children older than 2 y, CMV-specific CD4-secreting IFNγ alone predominated over CD4-secreting IL2 + IFNγ and a continuous increase, with aging, in IFNγ responses to the virus was observed. In contrast, in AdV infection, CD4-secreting IL2 + IFNγ predominated and IFNγ responses to the virus reached adult levels from 3 y of age. iii) In children aged 0-2 y, lower total IFNγ responses to CMV (p < 0.02), AdV (p = 0.05), and CD3 (p < 0.01) and lower IFNγ + IL2-responses (p = 0.1, p < 0.02, p < 0.05, respectively) contrasted with no decrease in CD4-secreting IFNγ alone. Defective proliferative responses to AdV (p = 0.03) were also observed. In conclusion, the development of memory CD4 differed in acute AdV and persistent CMV infections. Young age seemed to depress mostly polyfunctional (IL2 + IFNγ secreting) CD4 in both infections.