T-cell help permits memory CD8 super(+) T-cell inflation during cytomegalovirus latency

CD4 super(+) T cells are implied to sustain CD8 super(+) T-cell responses during persistent infections. As CD4 super(+) T cells are often themselves antiviral effectors, they might shape CD8 super(+) T-cell responses via help or via controlling antigen load. We used persistent murine CMV (MCMV) infection to dissect the impact of CD4 super(+) T cells on virus-specific CD8 super(+) T cells, distinguishing between increased viral load in the absence of CD4 super(+) T cells and CD4 super(+) T-cell-mediated helper mechanisms. Absence of T-helper cells was associated with sustained lytic MCMV replication and led to a slow and gradual reduction of the size and function of the MCMV-specific CD8 super(+) T-cell pool. However, when virus replication was controlled in the absence of CD4 super(+) T cells, CD8 super(+) T-cell function was comparably impaired, but in addition CD8 super(+) T-cell inflation, a hallmark of CMV infection, was completely abolished. Thus, CD8 super(+) T-cell inflation during latent CMV infection is strongly dependent on CD4 super(+) T-cell helper functions, which can partially be compensated by ongoing lytic viral replication in the absence of CD4 super(+) T cells.