Enhanced establishment of a virus carrier state in adult CD4⁺ T-cell-deficient mice

Abstract

CD4+ T cells play an important role in regulating the immune response; their contribution to virus clearance is variable. Mice that lack CD4+ T cells (CD4(-/-) mice) and are therefore unable to produce neutralizing antibodies cleared viscero-lymphotropic lymphocytic choriomeningitis virus (LCMV) strain WE when infected intravenously with a low dose (2 x 102 PFU) because of an effective CD8+ cytotoxic T-cell (CTL) response. In contrast, infection with a high dose (2 x 106 PFU) of LCMV strain WE led to expansion of antiviral CTL, which disappeared in CD4(-/-) mice; in contrast, CD4+ T- cell competent mice developed antiviral memory CTL. This exhaustion of specific CTL caused viral persistence in CD4(-/-) mice, whereas CD4+ T- cell-competent mice eliminated the virus. After infection of CD4(-/-) mice with the faster-replicating LCMV strain DOCILE, abrogation of CTL response and establishment of viral persistence developed after infection with a low dose (5 x 102 PFU), i.e., an about 100-fold lower dose than in CD4+- competent control mice. These results show that absence of T help enhances establishment of an LCMV carrier state in selected situations.