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.