Superiority of antibody versus delayed hypersensitivity in clearance of HSV-1 from eye.

Abstract

The contribution that antibody and delayed type hypersensitivity (DTH) make in promoting HSV-1 clearance from the infected cornea was investigated. Balb/c mice were immunized intravenously or subcutaneously with an attenuated strain of HSV-1 to generate hosts which were antibody-producing DTH-tolerant or antibody-producing DTH-responsive. Anti-mu serum treated mice were likewise sensitized intravenously or subcutaneously to obtain hosts which were antibody depressed-DTH tolerant or antibody-depressed DTH-responsive. Eight days after sensitization, these four sensitized groups and unsensitized controls were infected on scarified corneas with a stromal keratitis inducing strain of HSV-1, and the extent of virus replication was determined 1, 3, and 7 days later. Very different results were obtained depending upon the host's immune status. Virus proliferated extensively (greater than 3-4 logs) in the eyes of nonimmune mice and antibody-depressed DTH-tolerant hosts during the first 3 days after infection. In striking contrast, HSV-1 could not be detected even 24 hr post challenge in antibody-producing DTH-tolerant mice. In fact, such mice cleared virus from the eye as efficiently as immunologically intact hosts. However, in mice with the reverse immune status, ie antibody-depressed DTH-responsive, virus growth was clearly evident (greater than 2-3 logs) during days 1-3, and only thereafter did complete clearance occur. These results indicate that in the sensitized host antibody is both independent of and significantly more effective than DTH in promoting HSV-1 eradication from the infected eye.