Immunologic Control of Mus musculus Papillomavirus Type 1

Persistent papillomas developed in ~10% of out-bred immune-competent skh-1 mice following muspv1 challenge of their tail,and in a similar fraction the papillomas were transient,suggesting potential as a model. however,papillomas only occurred in balb/c or c57bl/6 mice depleted of t cells with anti-cd3 antibody,and they completely regressed within 8 weeks after depletion was stopped. neither cd4+ nor cd8+ t cell depletion alone in balb/c or c57bl/6 mice was sufficient to permit visible papilloma formation. however,low levels of muspv1 were sporadically detected by either genomic dna-specific pcr analysis of local skin swabs or in situ hybridization of the challenge site with an e6/e7 probe. after switching to cd3+ t cell depletion,papillomas appeared upon 14/15 of mice that had been cd4+ t cell depleted throughout the challenge phase,1/15 of cd8+ t cell depleted mice,and none in mice without any prior t cell depletion. both control animals and those depleted with cd8-specific antibody generated muspv1 l1 capsid-specific antibodies,but not those depleted with cd4-specific antibody prior to t cell depletion with cd3 antibody. thus,normal balb/c or c57bl/6 mice eliminate the challenge dose,whereas infection is suppressed but not completely cleared if their cd4 or cd8 t cells are depleted,and recrudescence of muspv1 is much greater in the former following treatment with cd3 antibody,possibly reflecting their failure to generate capsid antibody. systemic vaccination of c57bl/6 mice with dna vectors expressing muspv1 e6 or e7 fused to calreticulin elicits potent cd8 t cell responses and these immunodominant cd8 t cell epitopes were mapped. adoptive transfer of a muspv1 e6-specific cd8+ t cell line controlled established muspv1 infection and papilloma in rag1-knockout mice. these findings suggest the potential of immunotherapy for hpv-related disease and the importance of host immunogenetics in the outcome of infection. © 2015 wang et al.