Development of Virus‐Specific CD4+T Cells on Reexposure to Varicella‐Zoster Virus

Immunity to childhood diseases is maintained for decades by mechanisms that, at present, are still unclear. We longitudinally studied immune responses in 16 adults exposed to children experiencing varicella (chicken pox). None of the individuals showed clinical signs of infection, and varicella-zoster virus (VZV) DNA could not be detected in peripheral blood or cultured from nasopharyngeal swabs. Exposure to VZV, however, induced expansion of antigen-specific CD4+ T cells in peripheral blood, with concomitant changes in cytotoxic CD8+ T cells and natural killer cells. VZV-specific memory CD4+ T cells were uniformly CD45RA− and enriched for CD27− cells. The virus-specific cells produced interferon-γ, tumor necrosis factor-α, and interleukin-2. These memory responses to VZV were compared with the primary immune responses of children experiencing varicella. VZV-specific memory CD4+ T cell responses largely resemble the primary immune response to VZV.