NK cell and DC interactions

doi:10.1016/j.it.2003.10.012

Trends in Immunology

Volume 25, Issue 1, January 2004, Pages 47-52

https://doi.org/10.1016/j.it.2003.10.012 Get rights and content

Abstract

Recent interest has focused on interactions between natural killer (NK) cells and dendritic cells (DCs). In vitro and in vivo studies have demonstrated various effects of NK–DC interactions, including activation and cytokine production, maturation of DCs and NK-cell lysis of certain autologous DCs. These interactions are important during an immune response in vivo, however, it remains unclear where in the body NK cells and DCs might interact and whether observed in vitro crosstalk between these cell types happens in vivo. We propose evidence for at least two potential locations of in vivo interactions for human NK cells and DCs, including sites of inflammation and lymph nodes.

Section snippets

NK cells and DCs in immunity

NK cells are the major lymphocytes of the innate immune response and, through their production of cytokines and lysis of transformed cells, are crucial for both controlling infection and immune surveillance [1]. Cell-surface NK receptors (NKRs) recognizing MHC class I and class I-like molecules signal for inhibitory and activating NK-cell function, thus enabling NK cells to ‘recognize’ and selectively lyse foreign or transformed or infected cells 2, 3. Two subsets of human NK cells, CD56^bright

NK–DC interactions

Several studies have shown evidence for NK–DC crosstalk resulting in cellular activation, maturation and even death. Early work by Fernandez et al. provided the first evidence of NK–DC interactions in vivo by demonstrating DC activation of NK-cell anti-tumor effects [8]. More recently, NK–DC interactions were shown to be important for optimal immune cell expansion and activation during viral infection in vivo [9]. Subsequently, several human studies have investigated the range of interactions

Where do NK cells and DCs meet?

The majority of the data regarding NK-cell and DC interactions make it clear that cell-to-cell contact is required for optimal co-stimulatory effects 8, 11, 12, 13, 20. Thus, in order for NK–DC interactions to occur in vivo, there must be a common meeting ground for NK cells and DCs. There are several ways this could occur, including the recruitment of both cells to the same location and/or one cell recruiting the other to a particular location.

Sites of inflammation: recruiting grounds for DCs and NK cells

One of the triggers for NK–DC meetings might be inflammation and in particular sites of infection. Cytokines and chemokines produced by resident DCs and other cell types could attract iDCs and NK cells to sites of inflammation and initial infection 21, 22. Indeed, skin samples from patients infected with the yeast Malassezia reveal increased numbers of NK cells in close proximity to DCs, providing the only evidence for NK–DC contact in the periphery in vivo [23].

Once there, DCs might activate

Crosstalk in lymph nodes

As opposed to recruitment of NK cells and DCs to the same location, an additional hypothesis for NK–DC meetings is that DCs might travel to NK cells, thereby alerting NK cells to the presence of infection. After encountering a pathogen, DCs undergo a maturation process by which they upregulate various activation receptors, including the chemokine receptor CCR7, and travel to LNs to present antigen to T lymphocytes [7]. An additional consequence of DC recruitment to LNs might be interactions

Clinical significance of NK–DC interactions

There is currently considerable excitement over potential DC-based therapies for human disease (e.g. tumor vaccines) 37, 38 and renewed interest in NK-cell clinical applications following elucidation of the basic inhibition and activation NKR mechanisms [39]. Crucial to the success of these clinical endeavors will be a complete understanding of how these cells interact at sites of disease, as well as their role in orchestrating innate and adaptive responses. In vivo murine studies have shown

Conclusion

Recent evidence has highlighted the importance of NK–DC interactions for NK-cell activation, DC maturation and immunoregulatory crosstalk. In vitro evidence has demonstrated communications ranging from cooperative stimulation to NK-cell lysis of DCs. Important questions remain about the physiologic site of NK–DC crosstalk in vivo (i.e. peripheral sites of inflammation or malignancy versus secondary lymphoid tissues) that could shed light on the varying quality of interactions demonstrated in

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Trends in Immunology

NK cell and DC interactions

Abstract

Section snippets

NK cells and DCs in immunity

NK–DC interactions

Where do NK cells and DCs meet?

Sites of inflammation: recruiting grounds for DCs and NK cells

Crosstalk in lymph nodes

Clinical significance of NK–DC interactions

Conclusion

Trends Immunol.

Blood

Blood

Curr. Opin. Immunol.

Cell. Immunol.

Trends Immunol.

J. Invest. Dermatol.

Blood

Immunity

Blood

Curr. Opin. Immunol.

Curr. Opin. Immunol.

Lancet Oncol.

Blood

Human natural killer cell receptors and signal transduction

Int. Rev. Immunol.

Activating receptors and coreceptors involved in human natural killer cell-mediated cytolysis

Annu. Rev. Immunol.

Sensing pathogens and tuning immune responses

Science

Dendritic cells directly trigger NK cell functions: cross-talk relevant in innate anti-tumor immune responses in vivo

Nat. Med.

Functional interactions between dendritic cells and NK cells during viral infection

Nat. Immunol.

Enhancement of human cord blood CD34+ cell-derived NK cell cytotoxicity by dendritic cells

J. Immunol.

Reciprocal activating interaction between natural killer cells and dendritic cells

J. Exp. Med.

Enhancement of human cord blood CD34⁺ cell-derived NK cell cytotoxicity by dendritic cells