Cellular immune response of fetuses to cytomegalovirus

Pediatr Res. 2004 Feb;55(2):280-6. doi: 10.1203/01.PDR.0000104150.85437.FE. Epub 2003 Nov 19.

Abstract

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.

MeSH terms

  • Antigens, Viral / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / virology*
  • Carcinogens / pharmacology
  • Cell Differentiation / immunology
  • Cytomegalovirus Infections / immunology*
  • Female
  • Fetal Blood / cytology
  • Fetal Blood / immunology
  • Fetus / immunology*
  • Fetus / virology*
  • Humans
  • Immunologic Memory / immunology
  • Interferon-gamma / metabolism
  • Ionomycin / pharmacology
  • Ionophores / pharmacology
  • Lymphocyte Activation / drug effects
  • Lymphocyte Subsets
  • Pregnancy
  • Tetradecanoylphorbol Acetate / pharmacology

Substances

  • Antigens, Viral
  • Carcinogens
  • Ionophores
  • Ionomycin
  • Interferon-gamma
  • Tetradecanoylphorbol Acetate