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.
Laboratory of Immunology, Robert Debré Hospital, Paris 75019, France.
Béatrice
B
Pédron
Valérie
V
Guérin
Debora Jorge
DJ
Cordeiro
Sonia
S
Masmoudi
Jean-Hugues
JH
Dalle
Ghislaine
G
Sterkers
D000256:Adenoviridae / Q000276:immunology*; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000375:Aging / Q000276:immunology*; D000911:Antibodies, Monoclonal; D017252:CD3 Complex / Q000276:immunology; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D049109:Cell Proliferation; D002648:Child; D002675:Child, Preschool; D003587:Cytomegalovirus / Q000276:immunology*; D005602:France; D006801:Humans; D007156:Immunologic Memory; D007223:Infant; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D019041:L-Selectin / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008213:Lymphocyte Activation
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; C508594:IL2 protein, human; D007376:Interleukin-2; D019041:L-Selectin; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens