title: Viral inoculum dose impacts memory T-cell inflation.
abstract: 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.
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, Leiden, The Netherlands.
authors.forename: Anke
authors.initials: A
authors.lastname: Redeker
authors.forename: Suzanne P M
authors.initials: SP
authors.lastname: Welten
authors.forename: Ramon
authors.initials: R
authors.lastname: Arens
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D049109:Cell Proliferation; D002478:Cells, Cultured; D005434:Flow Cytometry; D006566:Herpesviridae Infections / Q000276:immunology* / Q000821:virology; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D016130:Immunophenotyping; D053699:Interleukin-7 Receptor alpha Subunit / Q000276:immunology / Q000378:metabolism; D019041:L-Selectin / Q000276:immunology / Q000378:metabolism; D037181:Lectins, C-Type; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018146:Muromegalovirus / Q000276:immunology* / Q000502:physiology; D011971:Receptors, Immunologic / Q000276:immunology / Q000378:metabolism; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000276:immunology / Q000378:metabolism; D017735:Virus Latency / Q000276:immunology
chemical_list: D053699:Interleukin-7 Receptor alpha Subunit; C451496:Klrg1 protein, mouse; D037181:Lectins, C-Type; D011971:Receptors, Immunologic; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D019041:L-Selectin
keywords: CD8+ T cells; CMV; Memory T-cell inflation; T-cell activation; Viral immunity