Clearance of HIV type 1 envelope recombinant sendai virus depends on CD4+ T cells and interferon-gamma but not B cells, CD8+ T cells, or perforin.

AIDS Research and Human Retroviruses
Sherri SurmanJulia L Hurwitz

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 (microMT) 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-gamma, 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-gamma), or (3) virus clearance. To determine if IFN-gamma was required for protection, we repeated experiments in IFN-gamma-KO animals. In this case, significant protection was lost, although the CD...Continue Reading

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Methods Mentioned

BETA
flow cytometry
FACS
dissection

Software Mentioned

GraphPad
GraphPad Prism
FlowJo

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