Protection against murine neonatal herpes simplex virus infection by lymphokine-treated human leukocytes

• Published in: The Journal of immunology (1950) Vol. 144; no. 1; pp. 307 - 312
• Main Author: KOHL, S
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Association of Immunologists 1990
• Subjects: Age Factors; Analysis of the immune response. Humoral and cellular immunity; Animals; Animals, Newborn; Antibodies, Viral - biosynthesis; Antibody-Dependent Cell Cytotoxicity - drug effects; Biological and medical sciences; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Herpes Simplex - prevention & control; Humans; Immunization, Passive; Immunobiology; In Vitro Techniques; Infant, Newborn; Interferon-gamma - pharmacology; Interleukin-2 - pharmacology; Killer Cells, Lymphokine-Activated - immunology; Leukocytes, Mononuclear; Mice; Organs and cells involved in the immune response; Recombinant Proteins; Simplexvirus - immunology; Human; Immunoprotection; Leukocyte; Herpesviridae; Alphaherpesvirinae; Rodentia; Cytokine; Herpes; Immune reconstitution; Adoptive transfer; Infection; Virus; Vertebrata; Mammalia; Mononuclear cell; Interleukin 2; Mouse; Viral disease; Newborn animal; Herpesvirus hominis; Lymphocyte; Gamma interferon; Macrophage
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.144.1.307

One-week-old mice were protected against a uniformly lethal herpes simplex virus (HSV) infection by IL-2 alone, but especially by the addition of human mononuclear cells (MC) plus IL-2. The dose response of IL-2 was biphasic. The addition of MC from cord blood did not enhance IL-2-mediated survival. Because the effect of IL-2 alone, or IL-2 plus MC, was ablated by anti-IFN-gamma and human neonates have an IFN-gamma production defect, the protective effect of MC plus human IFN-gamma (HuIFN-gamma) was tested. MC from adults cultured for 5 days in HuIFN-gamma afforded protection. At least 1 x 10(6) HuIFN-gamma-treated MC were required with increasing survival to 1 x 10(7) MC. The effector cell activity was ablated by adherence, silica, L-leucine methyl ester treatment or treatment with Leu-M3 plus C (all macrophage markers), and OKT4 plus C treatment (CD4 marker). Use of Leu-11, Leu-7, OKT3, or OKT8 plus C did not inhibit protection and excluded NK or T cell participation. In addition to survival, the ability to produce anti-HSV antibody was reconstituted. For the first time protection was afforded by human cord blood MC after treatment with HuIFN in vitro. We have identified an IFN-gamma-driven protection system against murine neonatal HSV infection mediated by human adult- or cord blood-derived CD4-positive macrophages. Protection is associated with enhanced effector cell function and reconstitution of the neonatal antibody production defect.