Defective production of anti-herpes simplex virus antibody by neonatal mice. Reconstitution with Ia+ macrophages and T helper lymphocytes from nonimmune adult syngeneic mice.
Both neonatal humans and mice are exquisitely susceptible to severe HSV infection. We have now documented a profound defect in the ability of neonatal C57BL/6 mice to produce anti-HSV ADCC antibody. This ability is acquired over the first 2 to 4 wk of life. Reconstitution of neonatal mice by i.p. injection of peritoneal cells from adult nonimmune syngeneic mice both affords dose-dependent protection against lethal HSV infection and reconstitutes the antibody-production defect. By cell-separation techniques (adherence, nylon wool column purification, B cell panning) and cell ablation techniques (silica treatment, irradiation, anti-T cell, anti-Ia, anti-Lyt-1.2 and anti-Lyt-2.2 monoclonal antibodies plus complement treatment) the subpopulations involved in the antibody production reconstitution of neonatal mice by adult cells were identified. These include both an Ia+, radioresistant, adherent, silica-sensitive macrophage population and a nylon wool column-purified, radiosensitive, anti-T, anti-Lyt-1.2-sensitive helper T cell population. The latter cell may be substituted for by concanavalin A-stimulated lymphokine-containing spleen cell supernatants or human recombinant IL 2. In addition to reconstitution of ADCC antibody production, the same cell populations, or cells plus lymphokine-containing supernatants or IL 2, protected the newborn mice from lethal HSV infection. Further characterization of this system and of soluble replacement factors has implications for therapy or immunoprophylaxis of human neonates with, or at risk of, HSV infection.
D000375:Aging; D000818:Animals; D000831:Animals, Newborn / Q000276:immunology*; D000914:Antibodies, Viral / Q000096:biosynthesis*; D000920:Antibody-Dependent Cell Cytotoxicity; D001402:B-Lymphocytes / Q000276:immunology; D002452:Cell Count; D006561:Herpes Simplex / Q000276:immunology / Q000401:mortality / Q000628:therapy; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D007153:Immunologic Deficiency Syndromes / Q000276:immunology* / Q000382:microbiology; D008264:Macrophages / Q000145:classification / Q000276:immunology / Q000637:transplantation*; D051379:Mice; D008810:Mice, Inbred C57BL; D010529:Peritoneal Cavity; D010641:Phenotype; D018139:Simplexvirus / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000637:transplantation*
D000914:Antibodies, Viral; D000949:Histocompatibility Antigens Class II