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Characterization of the human newborn response to herpesvirus antigen
Insights
Newborns have intact immune cell processing but a low frequency of herpesvirus-specific T cells, contributing to their susceptibility to severe viral infections. This highlights a key difference in neonatal immunity compared to older children and adults.
Area of Science:
- Immunology
- Virology
- Neonatal Research
Background:
- Neonates are highly susceptible to severe herpes simplex virus (HSV), cytomegalovirus (CMV), and varicella zoster virus (VZV) infections.
- Understanding the cellular immune response in newborns is crucial for explaining this vulnerability.
Purpose of the Study:
- To investigate the cellular immune response of human newborns to HSV, CMV, and VZV.
- To determine if newborns possess intact antigen-processing capabilities and to quantify herpesvirus-specific T cell frequencies.
Main Methods:
- Cultured newborn mononuclear cells with maternal T cell blasts specific for HSV, CMV, or VZV.
- Utilized limiting dilution cultures to assess T cell responder cell frequency (RCF) in newborns and compare with adults and children.
- Focused on T4+ lymphocyte subset responses.
Main Results:
- Newborn monocytes demonstrated intact antigen-processing capability, supporting maternal T cell proliferation.
- A very low frequency of herpesvirus-specific T cells (less than 1:1,400,000) was found in nonimmune newborns.
- Responder cell frequencies in adults and children with prior HSV or CMV exposure were significantly higher.
Conclusions:
- Newborns possess functional antigen-presenting cells for herpesviruses.
- The low frequency of virus-specific T cells in neonates is a significant factor in their deficient viral immunity.
- Immunity to HSV acquired post-neonatal period leads to increased T cell responder frequencies comparable to adults.
Abstract:
An investigation was made into the human newborn cellular response to herpes simplex virus type 1 (HSV), cytomegalovirus (CMV), and varicella zoster virus (VZV) to understand more about the nature of the neonate's susceptibility to overwhelming infection by these viruses. Newborn mononuclear cells sustained the proliferation in culture of maternal (i.e., haplotype-matched) T cell blasts with specificity for HSV, CMV, or VZV (p less than 0.05). This is evidence for intact antigen-processing capability by newborn monocytes. The response of the maternal T cell blasts appeared to be HLA-haplotype-restricted as suggested by experiments in which maternal T cell blasts were limited in number. Our culture conditions elicited responses predominantly from the T4+ lymphocyte subset. A low frequency of herpesvirus-specific T4+ lymphocytes in newborn blood might contribute to deficient viral immunity, so we evaluated the virus-specific T cell responding frequency in human newborns in limiting dilution cultures. We were unable to find a herpesvirus-specific responder cell frequency greater than 1:1,400,000 in nonimmune newborns. Three of seven adults who had no serum antibody to CMV had a CMV responder cell frequency (RCF) of 1:100,000 to 1:200,000. The RCF to HSV in immune children, ages 18 mo to 12 yr, and adults, ages 13 to 80 yr, ranged from 1:14,000 to 1:18,000. We conclude that newborn monocyte processing of herpesvirus antigen is intact, that T cell RCF is low in neonates, and that immunity to HSV after infection outside the newborn period results in comparable RCF between adults and children.