title: MyD88 plays a critical T cell-intrinsic role in supporting CD8 T cell expansion during acute lymphocytic choriomeningitis virus infection.
abstract: During acute lymphocytic choriomeningitis virus (LCMV) infection, CD8 T cells rapidly expand and differentiate into effectors that are required for viral clearance. The accumulation of activated T cells is greatly reduced in mice lacking the adaptor molecule MyD88. Although MyD88 has generally been considered to indirectly regulate adaptive immune responses by controlling inflammatory cytokine production and Ag presentation in innate immune cells, in this study, we identify an unappreciated cell-intrinsic role for MyD88 in LCMV-specific CD8 T cells. Using reciprocal adoptive transfer models and bone marrow chimeras, we show that Myd88(-/-) CD8 T cells are defective in their clonal expansion in response to LCMV infection, independent of their environment. Furthermore, we show that while MyD88 is dispensable for initial activation and division of LCMV-specific CD8 T cells during the early stages of viral infection, MyD88-dependent signals are critical for supporting their survival and sustained accumulation.
authors.affiliation: Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia PA 19104, USA.
authors.forename: Adeeb H
authors.initials: AH
authors.lastname: Rahman
authors.forename: Weiguo
authors.initials: W
authors.lastname: Cui
authors.forename: David F
authors.initials: DF
authors.lastname: Larosa
authors.forename: Devon K
authors.initials: DK
authors.lastname: Taylor
authors.forename: Jidong
authors.initials: J
authors.lastname: Zhang
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Goldstein
authors.forename: E John
authors.initials: EJ
authors.lastname: Wherry
authors.forename: Susan M
authors.initials: SM
authors.lastname: Kaech
authors.forename: Laurence A
authors.initials: LA
authors.lastname: Turka