Delayed type hypersensitivity to human cytomegalovirus

Abstract

A skin test for immunity to human cytomegalovirus (HCMV) is described in which skin induration is measured after intradermal injection of antigen derived from heat-inactivated Towne strain HCMV or of envelope prepared from the virus. Randomly selected healthy young adult males and females were prescreened for evidence of past infection with HCMV using serologic tests. Each individual was inoculated with heat inactivated whole virion HCMV antigen prepared from serum-free supernatants of HCMV-infected MRC-5 cells, non-infected MRC-5 cell lysates, and Candida extract. HCMV seropositive individuals developed positive skin reactions to both the Candida extract and the HCMV test antigen. No response was observed at the MRC-5 cell lysate inoculation site. The envelope antigen also elicited a response in seropositive individuals. Seronegative individuals who were negative to the HCMV intradermal antigen at the start of the study developed a positive response 1 week after subcutaneous immunization with live attenuated Towne strain HCMV. This response also correlated with the onset of in vitro proliferation responses to HCMV antigens by peripheral blood lymphocytes obtained from the immunized individuals. Furthermore, skin test and lymphocyte proliferation responses remained positive when tested up to 93 days post-immunization. In guinea pig experiments with HCMV, those animals immunized with purified HCMV or a virus envelope preparation developed strong skin reactions to intradermal injection of each of those antigens. In contrast, no reaction was observed in immune animals, either to viral capsid antigen or uninfected cell-lysate antigen, and no reactions were observed to any HCMV antigen in non-immune animals.