The cytolytic T lymphocyte response to the murine cytomegalovirus. I. Distinct maturation stages of cytolytic T lymphocytes constitute the cellular immune response during acute infection of mice with the murine cytomegalovirus.

Limiting dilution (LD) analysis with two modifications, the expansion and the restimulation LD assay, led to the detection and quantification of two distinct in vivo maturation stages within the lineage of virus-specific self-restricted CTL after infection of mice with the murine cytomegalovirus (MCMV). A low frequency set, representing an average of 15% of the specifically activated CTL-P in a draining lymph node, generated virus-specific lytic activity in the absence of antigen, solely under expansion conditions provided by growth and differentiation interleukins. These cells were considered to be active and were denoted antigen-independent or interleukin-receptive CTL-P (IL-CTL-P). A high frequency set required additional antigen in vitro to generate functionally active clones, and therefore the cells were termed antigen-dependent. Both sets are present in vivo simultaneously at the peak of the acute immune response and represent antigen-activated cells because their existence strictly depends on a preceding priming event. IL-CTL-P disappear quickly after acute infection and are absent during the memory state. It is proposed that the isolation of IL-CTL-P could serve to detect viral antigen expression during persistent and/or recurrent herpes virus infections.