Dendritic cell interactions

The initial indication that the fiinction(s) of lung IXls may be regulated by local Macs came from our initial studies on the isolation of peripheral lung DCs from the rat. These experiments identified the most potent APC population in coUagenase digest of parenchymal lung tissue as DCs, but further demonstrated that expression of their fidl APC potential required initial elimination of contaminating Macs (Holt et al., 1985). Similar results were obtained with airway epithelial DCs (Holt et al., 1988). 

More recent studies from our lab demonstrate that the capacity of lung and airway DCs to upregulate their APC functions and to acquire potent presentation capacity in response to GM-CSF in vitro, is inhibited by soluble signal(s) from the dominant local Mac population (PAMs), which include NO and TNFa (Holt et al., 1993). This mechanism also appears operative in vivo, as PAM elimination by the macrophage suicide technique , involving intratracheal administration of DMDP in liposomes, results in the rapid upregulation of the APC activity of resident lung DCs to approximate that achieved in vitro by co-culture with GM-CSF (Holt etal., 1993 Fig. 1.6). 

Macropht e-Dendritic Cell Emulation of T Cell Function(s) in Inflamed Lunpf and Airway Tissues 

Additionally, it is clear that a consistent feature of diseases such as asthma is the recruitment of monocytes into the alveolar spaces and the airway mucosa (Beasley etal., 1989 Poston etal., 1992). Monocytes are potent APCs for reactivation of primed T cells, and these cells additionally secrete cytokines such as GM-CSF and IL-1. 

TGF/3 and TNFa secretion by resident lung Macs is also a feature of lung and airway inflammation, in a variety of models (Becker aal., 1989 Khalil et al., 1989 Kips et al., 1992). 

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Barron, M. A., Blyveis, N., Pan, S. C., and Wilson, C. C. (2006), Human dendritic cell interactions with whole recombinant yeasts Implication for HIV-1 vaccine development, J. Clin. Immunol., 26,251-264. 

Dendritic Cells 1 2. Macrophage-Dendritic Cell Interactions 8... 

Shakhar G, Lindquist RL, Skokos D, Dudziak D, Huang JH, Nussenzweig MC, Dustin ML (2005) Stable T cell-dendritic cell interactions precede the development of both tolerance and immunity in vivo. Nat Immunol 6 707-714... 

Macrophage dendritic cell interaction in the regulation of the IgE response in asthma. Clinical and Experimental Allergy, 23, 4-6. 

FIGURE 14.11 Dendritic cells and the other cells of the immune system. This figure shows a rat dendritic cell interacting with a T cell. Through these interactions, the dendritic cells teach the acquired-immunity system what to attack. 

Granelli-Piperno A, Moser B, Pope M, Chen D, Wei Y, IsdeU F, O Doherty U, Paxton W, Koup R, Mojsov S, Bhardwaj N, Clark-Lewis I, BaggioUni M, Steinman RM (1996) Efficient interaction of HIV-1 with purified dendritic cells via multiple chemokine coreceptors. J Exp Med 184 2433-2438... 

Gombert M, Dieu-Nosjean MC, Winterberg F, et al. CCL1-CCR8 interactions an axis mediating the recruitment of T cells and Langerhans-type dendritic cells to sites of atopic skin inflammation. J Immunol 2005 174(8) 5082-5091. 

Granelli-Pipemo A, Moser B, Pope M, et al. Efficient interaction of HIV-1 with purified dendritic cells via multiple chemokine coreceptors. J Exp Med 1996 184 2433-2438. 

Hlavacek WS, Percus JK, Percus OE et al (2002) Retention of antigen on follicular dendritic cells and Blymphocytes through complement-mediated multivalent ligand-receptor interactions theory and application to HIV treatment. Math Biosci 176 185-202... 

Babensee JE (2007) Interaction of dendritic cells with biomaterials. Semin Immunol 20 101-108... 

Jilek S, Merkle HP, Walter E (2005) DNA-loaded biodegradable microparticles as vaccine delivery systems and their interaction with dendritic cells. Adv Drug Deliv Rev 57 377-390... 

Stagg AJ, Hart AL, Knight SC, Kamm MA Microbial-gut interactions in health and disease. Interactions between dendritic cells and bacteria in the regulation of intestinal immunity. Best Pract Res Clin Gastroenterol 2004 18 255-270. 

Nature of interactions with, and processing by, dendritic cells and other antigen... 

The mechanisms of autoimmunity may also entail interaction with MHC structures determined by the HLA alleles. Individuals carrying certain HLA alleles have been shown to be predisposed to certain autoimmune diseases, which may account in part for the genetic variability of autoimmunity. In addition, metabolites of a particular drug may vary between individuals to confound the development of drug-induced autoimmunity. Dendritic cells, such as the Langerhans cells of the skin and B lymphocytes that function to present antigens to Th cells, express class-II... 

Huh JC, Strickland DH, Jahnsen FL, Turner DJ, Thomas JA, Napoli S, Tobagus I, Stumbles PA, Sly PD, Holt PG Bidirectional interactions between antigen-bearing respiratory tract dendritic cells (DCs) and T cells precede the late phase reaction in experimental asthma DC activation occurs in the airway mucosa but not in the lung parenchyma. J Exp Med 2003 198 19-30. 

IL-23 has recently been shown to be produced by dendritic cells and by human cultured keratinocytes in healthy skin and in psoriasis - its role in atopic dermatitis has to be defined [22]. Interaction of keratinocytes with activated T cells via CD40-CD40L may enhance IL-23 production and subsequently the IFN-y production by memory T cells [23]. 

Oriss TB, Ostroukhova M, Seguin-Devaux C, Dixon-McCarthy B, Stolz DB, Watkins SC, Pillemer B, Ray P, Ray A Dynamics of dendritic cell phenotype and interactions with CD4 + T cells in airway inflammation and tolerance. J Immunol 2005 174 854-863. 

The class II proteins are produced mainly within specific cells, known as antigen-presenting cells (APC). Their role is to prepare antigens derived from the pathogens in such a way that they can interact with the T-helper cell receptor. Since this is their only role, they are sometimes called professional antigen-presenting cells , i.e. other immune cells can also present peptides to T-helper cells (e.g. macrophages, B-lymphocytes) but this is not their prime role. The professional APCs are also known as dendritic cells. 

The lymph node microenvironment represents a niche where CLL cells interact with different types of cells including monocyte-derived nurse-like cells (NLC), CD3+ CD4+ CD154+ T cells, mesenchymal stromal cells, dendritic cells, and endothelial cells (15). In addition to cell-cell interactions, CLL cells are also exposed to a variety of soluble factors such as antigens, cytokines, and chemokines (2). It is the combination of such signals that renders CLL cells less susceptible to chemotherapy and promotes clonal evolution and drug resistance. Thus, the role of the microenvironment needs to be carefully considered in order to develop novel and more effective therapies for CLL treatment (16). In particular, the efficacy of new drugs must be evaluated under experimental conditions that recapitulate (or at least partially mimic) the CLL microenvironment. 

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