Stacie N. Woolard

Natural Killer Cells as Novel Helpers in Anti-Herpes Simplex Virus Immune Response

ABSTRACT Innate defenses help to eliminate infection, but some of them also play a major role in shaping the magnitude and efficacy of the adaptive immune response. With regard to influencing subsequent adaptive immunity, NK cells aided by dendritic cells may be the most relevant components of the innate reaction to herpes simplex virus (HSV) infection. We confirm that mice lacking or depleted of NK cells are susceptible to HSV-induced lesions. The quantity and quality of CD8+ cytotoxic T lymphocytes generated in the absence of NK cells were diminished, thereby contributing to susceptibility to HSV-induced encephalitis. We demonstrate a novel helper role for NK cells, in that NK cells compensate for the loss of CD4 helper T cells and NK cell supplementation enhances the function of wild type anti-HSV CD8 T cells. In addition, NK cells were able to partially rescue the dysfunctional CD8+ T cells generated in the absence of CD4 T helper cells, thereby performing a novel rescue function. Hence, NK cells may well be exploited for enhancing and rescuing the T-cell response in situations where the CD4 helper response is affected.

Viral Vaccines and CTL Response

Immune induction by successful vaccine formulations seems to involve stimulation of both humoral and cellular arms of immunity. Nevertheless, CD8+ CTLs are of critical relevance in the context of intracellular infection and tumor for many reasons. The task of exerting antipathogen activity by CD8+ T cells, which principally function to control and eradicate intracellular pathogens, is enabled by constitutive expression of MHC class-I molecules on all tissue types. CTL induction offers hope for vaccines against pathogens that are resistant to neutralizing activity. This review discusses the mechanism of immune induction by some successful vaccines and based on the accrued evidence suggests ideas for improved design of CTL-inducing vaccines.

Herpes Simplex Virus Induces the Early Activation of NK Cell via MyD88- Dependent Signal~!2009-12-24~!2010-05-14~!2010-06-22~!

In the course of a Herpes Simples Virus type-1 (HSV-1) infection, the bidirectional cross-talk between Natural Killer (NK) cells and Dendritic Cells (DCs) is imperative in mounting an efficient immunological response. Enhanced DC maturation by Toll-Like Receptor (TLR) ligands is considered as a pivotal link between innate and adaptive immune responses, yet the impact of direct TLR signaling on NK:DC interaction during an HSV infection has yet to be examined. We demonstrate that HSV mediates the activation of NK cells and the induction of the cooperative relationship between NK cells and DCs via TLR. During the course of an HSV infection, the initial response required both types of innate cells and demonstrated phenotypic and functional activation much like that of TLR-stimulated cells. Using a MyD88 knock-out system diminished the early interaction between DCs and NK after HSV exposure. Our results indicate that HSV TLR- ligands modulate the early NK: DC interaction and may be a mechanism used by these innate immune cells to overcome virus mediated immune evasion and the initiation of a potent acquired immune response.