Sensory neurons regulate the effector functions of CD8+ T cells in controlling HSV-1 latency ex vivo.
We provide evidence that sensory neurons regulate the effector functions and phenotype of CD8+ T cells during active immunosurveillance of HSV-1 latency. Low-level viral gene expression in latently infected sensory ganglia gives rise to a unique, functionally active CD8+ T cell population. Surprisingly, distinct neuronal subsets require different CD8 effector mechanisms to maintain viral latency, with some requiring IFN-gamma and others requiring lytic granules (LG). This nonredundant efficacy of CD8+ T cell effector mechanisms in maintaining viral latency is explained as follows: (1) a subset of neurons that expresses IFN-gamma receptors (IFN-gamma R+) and Qa 1 responds to IFN-gamma, but Qa 1 engagement of CD94/NKG2a blocks LG exocytosis by CD8+ T cells; (2) another neuronal subset is responsive to LG because it lacks Qa 1 and is refractory to IFN-gamma because it also lacks IFN-gamma R. In the latter subset, LG appear to provide a nonlethal block of viral reactivation.
Prabhakaran
Kartik
K
Graduate Program in Immunology, University of Pittsburgh School of Medicine, 203 Lothrop Street, Pittsburgh, Pennsylvania 15213, USA.
Sheridan
Brian S
BS
Kinchington
Paul R
PR
Khanna
Kamal M
KM
Decman
Vilma
V
Lathrop
Kira
K
Hendricks
Robert L
RL
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D018259:Herpesvirus 1, Human / Q000502:physiology*; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism / Q000502:physiology* / Q000821:virology*; D010641:Phenotype; D014775:Virus Activation; D017735:Virus Latency
D007371:Interferon-gamma