Clearance of HIV Type 1 Envelope Recombinant Sendai Virus Depends on CD4 + T Cells and Interferon-γ But Not B Cells,CD8 + T Cells,or Perforin

Abstract

T cell-mediated viral clearance is classically attributed to the CD8⁺ T cell subset, but CD4⁺ T cells can sometimes assume this role. One such instance was illustrated by the immunization of C57BL/6 mice with HIV-1 envelope, followed by challenge with a recombinant Sendai virus (rSeV-env) carrying a gene for secreted HIV-1 envelope protein. Vaccinated mice that lacked both B cells (μMT) and CD8⁺ T cells controlled virus, but control was lost when CD4⁺ T cells were depleted. To explain this activity, we questioned whether CD4⁺ T cells might utilize perforin for killing of MHC class II-positive targets. We also asked if the process might depend on IFN-γ, which can upregulate MHC expression and enhance T cell recruitment to sites of virus challenge. To address these possibilities, we vaccinated perforin-KO mice with HIV-1 envelope and challenged them with rSeV-env. We found that perforin was not required for (1) CD4⁺ T cell homing to the site of virus challenge, (2) expression of Th1 and Th2 cytokines (including IFN-γ), or (3) virus clearance. To determine if IFN-γ was required for protection, we repeated experiments in IFN-γ-KO animals. In this case, significant protection was lost, although the CD4⁺ T cells trafficked readily to the site of infection. In fact, local CD4⁺ T cell numbers in vaccinated IFN-γ- KO mice exceeded those in wild type animals. In both cases, cells were αß TCR⁺, NK-1.1^–, and CD44⁺, typifying an activated CD4⁺ T cell subset. Taken together, our results showed that HIV-1 envelope recombinant virus clearance was dependent on CD4⁺ T cells and IFN-γ, but occurred in the absence of B cells, CD8⁺ T cells, or perforin.