Protection against murine neonatal herpes simplex virus infection by lymphokine-treated human leukocytes.
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.
Kohl
S
S
Department of Pediatrics, University of California Medical School, San Francisco General Hospital 94110.
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D000914:Antibodies, Viral / Q000096:biosynthesis; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects; D006561:Herpes Simplex / Q000517:prevention & control*; D006801:Humans; D007116:Immunization, Passive; D066298:In Vitro Techniques; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology*; D007963:Leukocytes, Mononuclear; D051379:Mice; D011994:Recombinant Proteins; D018139:Simplexvirus / Q000276:immunology*
D000914:Antibodies, Viral; D007376:Interleukin-2; D011994:Recombinant Proteins; D007371:Interferon-gamma