title: Comparing the kinetics of NK cells, CD4, and CD8 T cells in murine cytomegalovirus infection.
abstract: NK cells recognize virus-infected cells with germline-encoded activating and inhibitory receptors that do not undergo genetic recombination or mutation. Accordingly, NK cells are often considered part of the innate immune response. The innate response comprises rapid early defenders that do not form immune memory. However, there is increasing evidence that experienced NK cells provide increased protection to secondary infection, a hallmark of the adaptive response. In this study, we compare the dynamics of the innate and adaptive immune responses by examining the kinetic profiles of the NK and T cell response to murine CMV infection. We find that, unexpectedly, the kinetics of NK cell proliferation is neither earlier nor faster than the CD4 or CD8 T cell response. Furthermore, early NK cell contraction after the peak of the response is slower than that of T cells. Finally, unlike T cells, experienced NK cells do not experience biphasic decay after the response peak, a trait associated with memory formation. Rather, NK cell contraction is continuous, constant, and returns to below endogenous preinfection levels. This indicates that the reason why Ag-experienced NK cells remain detectable for a prolonged period after adoptive transfer and infection is in part due to the high precursor frequency, slow decay rate, and low background levels of Ly49H(+) NK cells in recipient DAP12-deficient mice. Thus, the quantitative contribution of Ag-experienced NK cells in an endogenous secondary response, with higher background levels of Ly49H(+) NK cells, may be not be as robust as the secondary response observed in T cells.
authors.affiliation: Complex Systems in Biology Group, Centre for Vascular Research, University of New South Wales, Kensington, New South Wales 2052, Australia.
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Schlub
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Sun
authors.forename: Senta M
authors.initials: SM
authors.lastname: Walton
authors.forename: Scott H
authors.initials: SH
authors.lastname: Robbins
authors.forename: Amelia K
authors.initials: AK
authors.lastname: Pinto
authors.forename: Michael W
authors.initials: MW
authors.lastname: Munks
authors.forename: Ann B
authors.initials: AB
authors.lastname: Hill
authors.forename: Laurent
authors.initials: L
authors.lastname: Brossay
authors.forename: Annette
authors.initials: A
authors.lastname: Oxenius
authors.forename: Miles P
authors.initials: MP
authors.lastname: Davenport
mesh_terms: D000818:Animals; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology* / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology* / Q000821:virology; D006566:Herpesviridae Infections / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D007156:Immunologic Memory; D007694:Killer Cells, Natural / Q000276:immunology* / Q000473:pathology* / Q000821:virology; D008099:Liver / Q000276:immunology / Q000473:pathology / Q000821:virology; D008168:Lung / Q000276:immunology / Q000473:pathology / Q000821:virology; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D018448:Models, Immunological; D018146:Muromegalovirus / Q000276:immunology*; D013154:Spleen / Q000276:immunology / Q000473:pathology / Q000821:virology; D013234:Stem Cells / Q000276:immunology / Q000473:pathology / Q000821:virology