ENHANCED ESTABLISHMENT OF A VIRUS CARRIER STATE IN ADULT CD4+ T-CELL-DEFICIENT MICE

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 10(2) PFU) because of an effective CD8(+) cytotoxic T-cell (CTL) response. In contrast, infection with a high dose (2 x 10(6) 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 10(2) 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.