Correlation of the Suppression of Mitogen Responsiveness and the Mixed Lymphocyte Reaction with the Proliferative Response to Viral Antigen of Splenic Lymphocytes from Cytomegalovirus-Infected Mice

Abstract

Lymphocyte function has been shown to be suppressed during cytomegalovirus infections of humans and mice. We compared nonspecific and specific lymphocyte reactions of splenic lymphocytes from murine cytomegalovirus (MCMV)-infected C3H adult mice during the acute and recovery phases of infection. The response to phytohemagglutinin or lipopolysaccharide was suppressed maximally 4 to 5 days after infection and returned to normal levels by 15 days. The mixed lymphocyte response was suppressed 2 to 10 days after infection and returned to normal by 15 days. In contrast, lymphocytes responded to MCMV-infected syngeneic mouse embryo fibroblasts (MEF) by day 2 of infection incorporating 52,183 ± 9866 counts per minute (cpm) of ³H-thymidine compared with 23,587 ± 3909 cpm with uninfected MEF. The response to infected MEF increased to 132,560 ± 27,739 cpm by day 10. The ability of splenic lymphocytes from infected mice to respond to MCMV-infected MEF was retained for at least 75 days after infection. Preliminary characterization of the cells responding in the MCMV-induced proliferation assay showed that they were sensitive to treatment with anti-θ serum and complement, but not to treatment with anti-mouse γ-globulin and complement. The development of a specific lymphocyte response to viral infected cells during MCMV infection at a time when the MLR and response to mitogens are suppressed suggests that viral induced immuno-suppression may result from the regulation of the immune response of the host rather than a direct effect of the virus.