Trends in Immunology
NK cell and DC interactions
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, CD56bright
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
References (43)
The biology of human natural killer-cell subsets
Trends Immunol.
(2001)CD56bright natural killer cells are present in human lymph nodes and are activated by T cell-derived IL-2: a potential new link between adaptive and innate immunity
Blood
(2003)- et al.
Interleukin 15: biology and relevance to human disease
Blood
(2001) - et al.
How dendritic cells and microbes interact to elicit or subvert protective immune responses
Curr. Opin. Immunol.
(2002) Peripheral blood dendritic cells, but not monocyte-derived dendritic cells, can augment human NK cell function
Cell. Immunol.
(2001)NK cells: a lesson from mismatched hematopoietic transplantation
Trends Immunol.
(2002)Natural killer and dendritic cell contact in lesional atopic dermatitis skin-Malassezia-influenced cell interaction
J. Invest. Dermatol.
(2002)In vivo evidence for a dependence on interleukin 15 for survival of natural killer cells
Blood
(2002)IL-15Ralpha recycles and presents IL-15 in trans to neighboring cells
Immunity
(2002)Dendritic cells for NK/LAK activation: rationale for multicellular immunotherapy in neuroblastoma patients
Blood
(2002)
Interferon-producing cells: on the front line in immune responses against pathogens
Curr. Opin. Immunol.
The dendritic cell and human cancer vaccines
Curr. Opin. Immunol.
The use of dendritic cells in cancer therapy
Lancet Oncol.
Natural killer cell receptors: new biology and insights into the graft-versus-leukemia effect
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.
Cited by (385)
Mesenchymal stem cells and allergic airway inflammation; a therapeutic approach to induce immunoregulatory responses
2023, International ImmunopharmacologyAnalysis of stochastic dynamics of tumor with drug interventions
2022, Chaos, Solitons and FractalsImmunosenescence and inflammaging in the aging process: age-related diseases or longevity?
2021, Ageing Research Reviews