title: Antiviral memory CD8 T-cell differentiation, maintenance, and secondary expansion occur independently of MyD88.
abstract: Inflammatory signals induced during infection regulate T-cell expansion, differentiation, and memory formation. Toll-like receptors (TLRs) are inflammatory mediators that allow innate immune cells to recognize and respond to invading pathogens. In addition to their role in innate immune cells, we have found that signals delivered through the TLR adapter protein myeloid differentiation protein 88 (MyD88) play a critical, T cell-intrinsic role in supporting the survival and accumulation of antigen-specific effector cells after acute viral infection. However, the importance of MyD88-dependent signals in regulating the generation and maintenance of memory T cells remained unclear. To address this, we used a novel, inducible knockout system to examine whether MyD88 is required for optimal memory CD8 T-cell generation and responses after lymphocytic choriomeningitis virus infection. We show that whereas MyD88 is critical for initial T-cell expansion, it is not required for the subsequent differentiation and stable maintenance of a memory T-cell population. Furthermore, in contrast to naive CD8 T cells, memory CD8 T cells do not depend on MyD88 for their secondary expansion. Our findings clarify the importance of MyD88 during distinct phases of the antiviral T-cell response and establish differential dependence on MyD88 signaling as a novel characteristic that distinguishes naive from memory CD8 T cells.
authors.affiliation: Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Adeeb H
authors.initials: AH
authors.lastname: Rahman
authors.forename: Ruan
authors.initials: R
authors.lastname: Zhang
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Blosser
authors.forename: Baidong
authors.initials: B
authors.lastname: Hou
authors.forename: Anthony L
authors.initials: AL
authors.lastname: Defranco
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Maltzman
authors.forename: E John
authors.initials: EJ
authors.lastname: Wherry
authors.forename: Laurence A
authors.initials: LA
authors.lastname: Turka
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000276:immunology*; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology*; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D017353:Gene Deletion; D007156:Immunologic Memory / Q000187:drug effects / Q000276:immunology*; D008216:Lymphocytic Choriomeningitis / Q000276:immunology / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology
chemical_list: D016207:Cytokines; D053594:Myeloid Differentiation Factor 88; D013629:Tamoxifen