NK cell–mediated killing of target cells triggers robust antigen-specific T cell–mediated and humoral responses

Krebs, Philippe; Barnes, Michael J.; Lampe, Kristin; Whitley, Karen S.; Bahjat, Keith S.; Beutler, Bruce; Janssen, Edith M.; Hoebe, Kasper

doi:10.1182/blood-2009-01-201467

Cited by 128 publications

(117 citation statements)

References 50 publications

Supporting

Mentioning

109

Contrasting

Order By: Relevance

“…NK cells represent a subset of innate immune cells that have been shown to play an important role in bridging innate and adaptive immune responses by influencing DC function (37), providing signals for augmenting Th1 immune responses (38)(39)(40), and inducing tumor-specific CTLs (41). In addition, it has been shown recently that NK cell-mediated cytotoxicity of Ag-expressing target cells induces robust Ag-specific adaptive immune responses (42). EAT-2 has been shown to be indispensable in activating NK cell-mediated cytotoxicity by acting as a downstream adapter protein facilitating signaling from the SLAM family receptor CRACC (in mice) (43,44) or NTB-A (in humans) (45).…”

Section: Discussionmentioning

confidence: 99%

Expression of the SLAM Family of Receptors Adapter EAT-2 as a Novel Strategy for Enhancing Beneficial Immune Responses to Vaccine Antigens

Aldhamen

Appledorn

Seregin

et al. 2011

The Journal of Immunology

View full text Add to dashboard Cite

Recent studies have shown that activation of the signaling lymphocytic activation molecule (SLAM) family of receptors plays an important role in several aspects of immune regulation. However, translation of this knowledge into a useful clinical application has not been undertaken. One important area where SLAM-mediated immune regulation may have keen importance is in the field of vaccinology. Because SLAM signaling plays such a critical role in the innate and adaptive immunity, we endeavored to develop a strategy to improve the efficacy of vaccines by incorporation of proteins known to be important in SLAM-mediated signaling. In this study, we hypothesized that coexpression of the SLAM adapter EWS-FLI1–activated transcript 2 (EAT-2) along with a pathogen-derived Ag would facilitate induction of beneficial innate immune responses, resulting in improved induction of Ag-specific adaptive immune responses. To test this hypothesis, we used rAd5 vector-based vaccines expressing murine EAT-2, or the HIV-1–derived Ag Gag. Compared with appropriate controls, rAd5 vectors expressing EAT-2 facilitated bystander activation of NK, NKT, B, and T cells early after their administration into animals. EAT-2 overexpression also augments the expression of APC (macrophages and dendritic cells) surface markers. Indeed, this multitiered activation of the innate immune system by vaccine-mediated EAT-2 expression enhanced the induction of Ag-specific cellular immune responses. Because both mice and humans express highly conserved EAT-2 adapters, our results suggest that human vaccination strategies that specifically facilitate SLAM signaling may improve vaccine potency when targeting HIV Ags specifically, as well as numerous other vaccine targets in general.

show abstract

Section: Discussionmentioning

confidence: 99%

Expression of the SLAM Family of Receptors Adapter EAT-2 as a Novel Strategy for Enhancing Beneficial Immune Responses to Vaccine Antigens

Aldhamen

Appledorn

Seregin

et al. 2011

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…It is more likely that destruction of HCV-infected hepatocytes by NK cells facilitates uptake of apoptotic bodies by migratory DCs and enhance antigen transfer to the lymph nodes and priming of HCV-specific CD4+ and CD8+ T cells. Indeed, a recent study in mice demonstrated that NK cell-mediated killing of target cells triggers antigen-specific CD8 + and CD4 + T cell-mediated and humoral responses [46]. In addition to killing infected and cancerous cells, NK cells can also kill immature DCs [9,47].…”

Section: Discussionmentioning

confidence: 99%

Increased degranulation of natural killer cells during acute HCV correlates with the magnitude of virus-specific T cell responses

Pelletier

Drouin

Bédard

et al. 2010

Journal of Hepatology

104

View full text Add to dashboard Cite

Background/Aims-Natural killer (NK) cells provide early defense against viral infections by killing infected cells and producing cytokines that inhibit viral replication. NK cells also interact with dendritic cells (DCs) and this reciprocal interaction regulates both innate and adaptive immunity. Genetic studies have suggested that NK cell activity is a determinant of HCV infectious outcome but a functional correlation was not established. We hypothesized that increased NK cell activity during acute HCV infection will correlate with spontaneous viral clearance.

show abstract

“…A s effector lymphocytes of the innate immune system, NK cells contribute to the first line of immune defense through the lysis of virus-infected and malignant cells. Furthermore, NK cells play an important role in the initiation, enhancement, and regulation of immune responses, directly through the secretion of cytokines and chemokines, as well as via their interaction with other innate immune cells (1)(2)(3)(4)(5)(6)(7)(8).…”

Section: 1mentioning

confidence: 99%

Human Lymphoid Tissues Harbor a Distinct CD69+CXCR6+ NK Cell Population

Lugthart

Melsen

Vervat

et al. 2016

The Journal of Immunology

122

View full text Add to dashboard Cite

Knowledge of human NK cells is based primarily on conventional CD56bright and CD56dim NK cells from blood. However, most cellular immune interactions occur in lymphoid organs. Based on the coexpression of CD69 and CXCR6, we identified a third major NK cell subset in lymphoid tissues. This population represents 30–60% of NK cells in marrow, spleen, and lymph node but is absent from blood. CD69+CXCR6+ lymphoid tissue NK cells have an intermediate expression of CD56 and high expression of NKp46 and ICAM-1. In contrast to circulating NK cells, they have a bimodal expression of the activating receptor DNAX accessory molecule 1. CD69+CXCR6+ NK cells do not express the early markers c-kit and IL-7Rα, nor killer cell Ig-like receptors or other late-differentiation markers. After cytokine stimulation, CD69+CXCR6+ NK cells produce IFN-γ at levels comparable to CD56dim NK cells. They constitutively express perforin but require preactivation to express granzyme B and exert cytotoxicity. After hematopoietic stem cell transplantation, CD69+CXCR6+ lymphoid tissue NK cells do not exhibit the hyperexpansion observed for both conventional NK cell populations. CD69+CXCR6+ NK cells constitute a separate NK cell population with a distinct phenotype and function. The identification of this NK cell population in lymphoid tissues provides tools to further evaluate the cellular interactions and role of NK cells in human immunity.

show abstract

NK cell–mediated killing of target cells triggers robust antigen-specific T cell–mediated and humoral responses

Cited by 128 publications

References 50 publications

Expression of the SLAM Family of Receptors Adapter EAT-2 as a Novel Strategy for Enhancing Beneficial Immune Responses to Vaccine Antigens

Expression of the SLAM Family of Receptors Adapter EAT-2 as a Novel Strategy for Enhancing Beneficial Immune Responses to Vaccine Antigens

Increased degranulation of natural killer cells during acute HCV correlates with the magnitude of virus-specific T cell responses

Human Lymphoid Tissues Harbor a Distinct CD69+CXCR6+ NK Cell Population

Contact Info

Product

Resources

About