Activated T lymphocytes from mice infected by lymphocytic choriomeningitis virus display high affinity IL-2 receptors but do not proliferate in response to IL-2

Abstract

The i.v. injection of mice with lymphocytic choriomeningitis virus (LCMV) initiates a rapid and long lasting immunodepression which can be monitored in vivo or in vitro. Splenic T lymphocytes taken from mice infected for 7 days with LCMV are characterized by a low proliferative capacity in response to Con A stimulation in vitro. In an initial attempt to understand the molecular mechanisms regulating the general anergy induced by the viral infection, we have analyzed the transcription of IL-2 and of p55 IL-2R alpha gene, two genes involved in T cell proliferation. IL-2 gene transcripts were hardly detected after Con A activation of spleen cells from LCMV-infected mice. In contrast, the expression of the gene encoding IL-2R alpha chain was induced as in control noninfected cells. In addition, the expression of the p75 IL-2R beta chain was not modified. The transcripts of the IL-2R alpha and of the IL-2R beta genes were normally translated as high affinity. IL-2R were expressed on the membrane of T lymphocytes from LCMV-infected mice. Despite the finding that these receptors could also internalize IL-2, the exogenous addition of this growth factor did not induce cell proliferation, indicating that the virus-induced blockade is multifocal.