Viral inoculum dose impacts memory T-cell inflation

Memory T-cell inflation develops during certain persistent viral infections and is characterized by the accumulation and maintenance of large numbers of effector-memory T cells, albeit with varying degrees in size and phenotype among infected hosts. The underlying mechanisms that control memory T-cell inflation are not yet fully understood. Here, we dissected CMV-specific memory T-cell formation and its connection to the initial infectious dose by varying the inoculum size. After low dose inoculum with mouse CMV, the accumulation of inflationary memory T cells was severely hampered and correlated with reduced reservoirs of latent virus in nonhematopoietic cells and diminished antigen-driven T-cell proliferation. Moreover, lowering of the initial viral dose turned the characteristic effector memory-like inflationary T cells into more central memory-like cells as evidenced by the cell-surface phenotype of CD27(high), CD62L(+), CD127(+), and KLRG1(-), and by improved secondary expansion potential. These data show the impact of the viral inoculum on the degree of memory T-cell inflation and provide a rationale for the observed variation of human CMV-specific T-cell responses in terms of magnitude and phenotype.