Cellular immune response of fetuses to cytomegalovirus.
Primary infection with cytomegalovirus (CMV) in immunocompetent hosts is accompanied with activation and differentiation of naive CD8(+) T cells to effector/memory cells secreting interferon-gamma (IFN-gamma). Alteration of these responses during the perinatal period is suggested by a higher rate of CMV diseases in congenital infection. For addressing this issue, immunologic investigations were performed in 15 fetuses (22-36 wk of gestation) with documented congenital CMV infection. Results show that cellular immune responses can be detected as soon as the 22nd week of gestation (the youngest fetus analyzed). Compared with age-matched control subjects, infected fetuses evidence a dramatic increase in the percentages of activated and terminally differentiated CD8 T cells. Indeed, median percentages (interquartile range) of HLA-DR(+) and of CD28(-)CD8(+) T cells were 24% (19-34) and 38% (24-52), respectively in infected fetuses versus 3% (0-4) for each subset in control subjects. In addition, the percentages of T cells secreting IFN-gamma after in vitro stimulation with phorbol myristate acetate and ionomycin was significantly higher in infected fetuses [10% (5-25)] than in healthy fetuses [0.8% (0.6-1.2)] with IFN-gamma being mostly secreted by CD8(+) T cells and to a lesser extend by CD4(+) T cells. These cellular immune responses have clear similarities with responses previously reported in adults. Cellular immunity to CMV, however, might not be fully functional in fetuses. Indeed, the number of T cells capable of secreting IFN-gamma is strikingly lower after in vitro stimulation with the CMV-specific antigen than after in vitro stimulation with phorbol myristate acetate/ionomycin that bypasses signaling through the T-cell receptor.
Elbou Ould
Mohamed Abdelhaye
MA
Laboratory of Immunology, Hôpital Robert Debré, 48 Boulevard Sérurier, 75019 Paris, France.
Luton
Dominique
D
Yadini
Mounia
M
Pedron
Béatrice
B
Aujard
Yannick
Y
Jacqz-Aigrain
Evelyn
E
Jacquemard
François
F
Sterkers
Ghislaine
G
D000956:Antigens, Viral / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D002273:Carcinogens / Q000494:pharmacology; D002454:Cell Differentiation / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000276:immunology*; D005260:Female; D005312:Fetal Blood / Q000166:cytology / Q000276:immunology; D005333:Fetus / Q000276:immunology* / Q000821:virology*; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D016131:Lymphocyte Subsets; D011247:Pregnancy; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000956:Antigens, Viral; D002273:Carcinogens; D007476:Ionophores; D015759:Ionomycin; D007371:Interferon-gamma; D013755:Tetradecanoylphorbol Acetate