RESUMO
Natural killer cytotoxicity (NKC) is an important early defense mechanism in viral infections. We determined the ability of interleukin-2 (IL-2), an NKC stimulator, to enhance defective neonatal NKC to virus-infected cells. Human recombinant IL-2-stimulated adult and cord blood NKC to herpes simplex virus-infected cells in a time-dependent and dose-dependent fashion. The highest level of neonatal IL-2-stimulated cytotoxicity approached the level of unstimulated cytotoxicity when adult cells are used. Single-cell experiments suggested that the cord blood defect was due not to decreased adherence but to lysis or recycling defects. IL-2 stimulated adhesion in the presence of antibody but had no stimulatory effect on antibody-dependent cellular cytotoxicity. The relative defects in IL-2 stimulation of neonatal NKC suggest that its lone use as a therapeutic or protective agent against herpes simplex virus infections is unlikely to be successful, and may require concomitant adult cells if NKC is a critical mechanism.
Assuntos
Recém-Nascido/imunologia , Interleucina-2/farmacologia , Células Matadoras Naturais/efeitos dos fármacos , Simplexvirus/imunologia , Adesão Celular/efeitos dos fármacos , Sangue Fetal/imunologia , Humanos , Técnicas In Vitro , Células Matadoras Naturais/imunologiaRESUMO
Low natural killer cytotoxicity has been associated with serious herpes simplex virus infections. Neonates' mononuclear cells had significantly lower NKC to HSV infected (P less than 0.001) and uninfected (P less than 0.005) target cells than did adults' MC. Under appropriate conditions, both neonates' MC to NKC was increased by exogenous human leukocyte interferon. Although neonates' and adults' MC had a similar sensitivity to interferon, there was a significant (P = 0.05) lack of consistency in neonates' MC response. Twenty-three percent (4/17) of neonates' MC samples did not respond with increased NKC in the presence of interferon, unlike adults' MC, all of which demonstrated increased NKC. Neonates' MC did not suppress adults' MC-NKC. These data demonstrate the efficacy of interferon as an NKC stimulator in the neonate, but indicate a heterogeneous response of neonatal cells. We are encouraged with the prospect of clinical trials of interferon to treat severe viral infections in neonates. We urge the inclusion of immune surveillance in these trials.