Normal development and function but impaired memory phenotype of CD8+ T cells in transgenic mice expressing HIV-1 Nef in its natural target cells

We studied the impact of HIV Nef on CD8+ T cells in a mouse model of AIDS, the CD4C/HIVNef transgenic (Tg) mice. We found that negative and positive thymic selections of CD8+ T cells proceeded normally in Nef Tg mice bred respectively with HY or OT-1 TCR Tg mice. Tg peripheral CD8+ T cells showed an activated phenotype and enhanced cell division in vivo and proliferated efficiently when stimulated in vitro with antigenic peptide. When challenged with LCMVArmstrong, Nef Tg mice developed a strong acute CD8+ T cell response and cleared the virus as efficiently as wild-type mice. However, maintenance of LCMV-specific CD8+ memory T cells was impaired in Nef Tg mice, a defect partially rescued by adoptive transfer of non-Tg naïve CD4+ T cells. Thus, despite severe abnormalities of their precursors, the double-positive CD4+CD8+ thymocytes, Tg CD8+ T cells have conserved important functions.

► Nef does not impair negative and positive thymic selections of CD8+ T cells.
► Nef does not impair acute CD8+ T cell response against LCMV.
► Nef impairs maintenance of LCMV-specific CD8+ memory T cells.