CD4 + T Cells Are Required for the Priming of CD8 + T Cells following Infection with Herpes Simplex Virus Type 1

Abstract

ABSTRACT The role of CD4 + helper T cells in modulating the acquired immune response to herpes simplex virus type 1 (HSV-1) remains ill defined; in particular, it is unclear whether CD4 + T cells are needed for the generation of the protective HSV-1-specific CD8 + -T-cell response. This study examined the contribution of CD4 + T cells in the generation of the primary CD8 + -T-cell responses following acute infection with HSV-1. The results demonstrate that the CD8 + -T-cell response generated in the draining lymph nodes of CD4 + -T-cell-depleted C57BL/6 mice and B6-MHC-II −/− mice is quantitatively and qualitatively distinct from the CD8 + T cells generated in normal C57BL/6 mice. Phenotypic analyses show that virus-specific CD8 + T cells express comparable levels of the activation marker CD44 in mice lacking CD4 + T cells and normal mice. In contrast, CD8 + T cells generated in the absence of CD4 + T cells express the interleukin 2 receptor α-chain (CD25) at lower levels. Importantly, the CD8 + T cells in the CD4 + -T-cell-deficient environment are functionally active with respect to the expression of cytolytic activity in vivo but exhibit a diminished capacity to produce gamma interferon and tumor necrosis factor alpha. Furthermore, the primary expansion of HSV-1-specific CD8 + T cells is diminished in the absence of CD4 + -T-cell help. These results suggest that CD4 + -T-cell help is essential for the generation of fully functional CD8 + T cells during the primary response to HSV-1 infection.