Cellular immunity in infectious mononucleosis. II. Specific reactivity to Epstein-Barr Virus antigens and correlation with clinical and hematologic parameters.

Infectious mononucleosis (IM) patients, Epstein-Barr virus (EBV)-seropositive and seronegative healthy donors, and patients with other viral infections were tested for lymphocyte blastogenesis (LB) with phytohemagglutinin and six EBV (virus concentrate, culture supernatant, and soluble [S] antigen) or control antigens. Fluorescent antibodies to EBV viral capsid antigen of IgG, IgM, IgA specificities, to nuclear antigen (EBNA), and heterophile antibodies were also assayed. These were correlated with clinical parameters (fever, pharyngitis, adenopathy, hepatitis, splenomegaly, atypical lymphocytes, and total mononuclear cell counts). EBV viral and S antigen-induced LB was significantly greater in seropositive donors. IM patients had antigenspecific LB below that of seropositive donors initially and low responses for the acute phase of illness when clinical symptoms were present and antibody titers were maximal. Specific LB rose to a peak at 3.5 to 9 weeks when the patients had recovered, most laboratory findings had returned to normal, and antibodies had declined. At peak, specific LB in IM patients exceeded that of seropositive donors, but later declined. These results demonstrate specific cell-mediated immunity (CMI) to EBV, and indicate that this develops slowly in IM and contrasts with the evolution of the clinical events and humoral immunity. This correlation supports the hypothesis that CMI is the mechanism of terminating lymphoproliferation in IM.