Effect of anti-herpesvirus drugs on human and bovine lymphoid function in vitro

Abstract

Lymphocyte proliferative responses to phytohemagglutinin, pokeweed mitogen, and herpesvirus (herpes simplex virus and infectious bovine rhinotracheitis virus) antigens were evaluated in the presence of various concentrations of the anti-herpesvirus drugs, methylmethoxydeoxyuridine (OCH3CH2UdR), cytosine arabinoside was inhibitory at 25 ug/ml and cytosine arabinoside was inhibitory OCH3CH2UdR per ml, lymphocyte proliferative responses were unaffected and were not abolished even by concentrations of 2,500 ,Lg/ml. In contrast, adenine arabinocide was inhibitory at 25 ,.g/ml and cytosine arabinoside was inhibitory at 5 ,ug/ml. Both direct and antibody-dependent lymphocyte cytotoxicity of herpesvirus-infected target cells were highly resistant to OCH3CH2UdR; concentrations of 1,000 ,ig/ml were only marginally inhibitory. The anti-herpesvirus activity of all three drugs is similar (0.5 to 8 ug/ml) (L. A. Babiuk, B. Meldrum, V. S. Gupta, and B. T. Rouse, submitted for publication). The drug OCH3CH2UdR should be given a careful, well-controlled evaluation of its effectiveness in the treatment of herpes simplex infections in animals, perhaps including humans, since our results using in vitro models show that cellular responses important for recovery from herpesvirus infections are unaffected by doses far in excess of those found to be antiviral.

The effect of anti-TfR mouse/human chimeric antibody on anti-transplant rejection

“…PBMCs were adjusted to 2 × 10 6 cells/ml. The expression of TfR in T cells (CD3+) after mitogen induction (25 μg/ml) [15] for 12, 36 or 60 h were analyzed by indirect immunofluorescence using a FACScan cytometer (Becton Dickinson, Franklin Lakes, NJ, USA) with Cellquest software.…”

Analysis of the Adhesion Step in the Herpes Simplex Virus Antibody-Dependent Cellular Cytotoxicity System

“…Tissue culture cells undergoing acute viral infection can be lysed in vitro by human peripheral blood mononuclear cells in the presence of antiviral antibody. This phenomenon of antibody-dependent cellular cytotoxicity (ADCC) against virus-infected cells was first demonstrated for herpes simplex virus (HSV) (29,31,35,38) but has since been extended to include several other DNA-containing (3,28) and RNAcontaining (2,16,20,26,33) viruses. Like other ADCC systems involving erythrocyte targets, the ADCC reaction for virus-infected tissue culture cells requires direct contact between target cells and effector cells (25,30,37) and takes place because of an interaction between the Fc epitopes of target cell-bound antibodies, usually of the immunoglobulin G (IgG) class, and the Fc receptors for IgG on the effector cells (21,24).…”

“…Like other ADCC systems involving erythrocyte targets, the ADCC reaction for virus-infected tissue culture cells requires direct contact between target cells and effector cells (25,30,37) and takes place because of an interaction between the Fc epitopes of target cell-bound antibodies, usually of the immunoglobulin G (IgG) class, and the Fc receptors for IgG on the effector cells (21,24). Although direct evidence for an in vivo role of ADCC in host defense against viral infections is sparse, antibody has been shown to act synergistically with mononuclear cells of either bovine or murine origin in inhibiting the replication of herpesviruses in monolayer cell cultures (3,34). In addition, several murine tumor models suggest that ADCC may be operative in tumor immunity (9,17).Relatively little is known about the precise mechanism by which effector cells destroy antibody-coated target cells.…”