CD4+ T cells are required for the maintenance, not programming, of memory CD8+ T cells after acute infection

Immunization in the absence of CD4+ T cell help results in defective CD8+ T cell memory, deficient recall responses and diminished protective immunity. Here we investigated at what stage during the immune response to pathogen CD4+ T cells are essential in the promotion of functional CD8+ T cell memory. Memory CD8+ T cell numbers decreased gradually in the absence of CD4+ T cells despite the presence of similar numbers of memory cell precursors at the peak of the effector phase. Adoptive transfer of effector or memory CD8+ T cells into wild-type or CD4+ T cell–deficient mice demonstrated that the presence of CD4+ T cells was important only after, not during, the early CD8+ T cell programming phase. In the absence of CD4+ T cells, memory CD8+ T cells became functionally impaired and decreased in quantity over time. We conclude that in the context of an acute infection, CD4+ T cells are required only during the maintenance phase of long-lived memory CD8+ T cells.