Strain-specific local and systemic cell-mediated immune responses to cytomegalovirus in humans

Employing the techniques of complement fixation, immunofluorescence, and in vitro lymphocyte transformation assay, the antibody and cell-mediated immunity to cytomegalovirus (CMV) were studied in the serum, peripheral blood lymphocytes, tonsillar lymphocytes, and cord blood lymphocytes. The study population consisted of 32 children undergoing tonsillectomy and adenoidectomy. In the lymphocyte transformation assay, three strains of CMV (AD-169, ADH-1-41, and Davis), herpes simplex type 1, and phytohemagglutinin were employed as antigens. Sixty-five percent of the subjects were found to have CMV-specific antibody activity. The lymphocyte transformation response to phytohemagglutinin was similar in all subjects. No CMV-specific lymphocyte transformation activity was detected in cultures of cord blood lymphocytes. Significant cell-mediated immunity was observed in the tonsillar lymphocytes of 30% (3/10) of the seronegative individuals and in the peripheral blood lymphocytes obtained from one such subject. Over 75% (16/21) of the seropositive subjects demonstrated cell-mediated immunity against one or more strains of CMV in the peripheral blood lymphocytes and tonsillar lymphocytes. In the lymphocyte transformation assay, no cross-reactivity was apparent between CMV and herpes simplex type 1. These studies demonstrate the presence of strain-specific systemic and mucosal cell-mediated immune response to CMV in humans. The frequency and distribution of lymphocyte transformation responses to the three CMV strains suggest antigenic heterogeneity of CMV.