scholarly journals Antigen-bearing dendritic cells from the sublingual mucosa recirculate to distant systemic lymphoid organs to prime mucosal CD8 T cells

2013 ◽  
Vol 7 (2) ◽  
pp. 280-291 ◽  
Author(s):  
C Hervouet ◽  
C Luci ◽  
S Bekri ◽  
T Juhel ◽  
F Bihl ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Cd8 T Cells ◽  
Lymphoid Organs ◽  
Sublingual Mucosa

scholarly journals Dendritic cells require NIK for CD40-dependent cross-priming of CD8+ T cells

2015 ◽  
Vol 112 (47) ◽  
pp. 14664-14669 ◽  
Author(s):  
Anand K. Katakam ◽  
Hans Brightbill ◽  
Christian Franci ◽  
Chung Kung ◽  
Victor Nunez ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Cd8 T Cells ◽  
Lymphoid Organs ◽  
Serine Threonine Kinase ◽  
Cross Presentation ◽  
Inflammatory Stimuli ◽  
Dc Maturation

Dendritic cells (DCs) link innate and adaptive immunity and use a host of innate immune and inflammatory receptors to respond to pathogens and inflammatory stimuli. Although DC maturation via canonical NF-κB signaling is critical for many of these functions, the role of noncanonical NF-κB signaling via the serine/threonine kinase NIK (NF-κB–inducing kinase) remains unclear. Because NIK-deficient mice lack secondary lymphoid organs, we generated transgenic mice with targeted NIK deletion in CD11c+ cells. Although these mice exhibited normal lymphoid organs, they were defective in cross-priming naive CD8+ T cells following vaccination, even in the presence of anti-CD40 or polyinosinic:polycytidylic acid to induce DC maturation. This impairment reflected two intrinsic defects observed in splenic CD8+ DCs in vitro, namely antigen cross-presentation to CD8+ T cells and secretion of IL-12p40, a cytokine known to promote cross-priming in vivo. In contrast, antigen presentation to CD4+ T cells was not affected. These findings reveal that NIK, and thus probably the noncanonical NF-κB pathway, is critical to allow DCs to acquire the capacity to cross-present antigen and prime CD8 T cells after exposure to licensing stimuli, such as an agonistic anti-CD40 antibody or Toll-like receptor 3 ligand.

The Lymphoid Chemokine CCL21 Enhances the Migration- and CTL-Inducing Functions of Dendritic Cells

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1127-1127
Author(s):  
Cheol Yi Hong ◽  
Pawel Kalinski ◽  
Hyeoung-Joon Kim ◽  
Je-Jung Lee
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Cd8 T Cells ◽  
Conflicts Of Interest ◽  
Cytotoxic T Cells ◽  
Lymphoid Organ ◽  
Lymphoid Organs ◽  
Dependent Manner ◽  
Migratory Capacity ◽  
Secondary Lymphoid Organs

Abstract Abstract 1127 The migration of dendritic cells (DCs) to secondary lymphoid organs is very important to elicit an adaptive immune response in cancer immunotherapy. Here, we show the effect of lymphoid cytokine on the ability of maturing DCs to migrate in response to the lymph node-associated chemokines. The secondary-lymphoid organ chemokine (SLC/CCL21) during DC maturation dramatically enhanced DC migratory capacity responding to CCL21 and CCL19, and, moreover, produced strongly enhanced cytotoxic T cells, although it did not affect the expression of cell surface markers such as CD80, CD83, CD86, and CCR7 and the production of cytokines such as IL-12p70, IL-10, and IL-23. Mature DCs (mDCs) exposed by chemokine produced higher levels of CXCL10 (IP-10) that is one of the chemokines involved in Th1 attraction, but did not affect the production of Th2-attracting cytokine CCL22, compared with unstimulated mDCs. CCL21-exposed DCs induced strongly enhanced numbers of the interferon-g (IFN-g)-expressing antigen-specific CD8+ T cells against tumor-specific antigens in an CXCL10-dependent manner. Cytotoxic CD8+ T cells stimulated with CCL21-exposed DCs expressed higher level of IFN-g than those stimulated with control mDCs. Interestingly, generation of cytotoxic T cells (CTLs) stimulated by TNFa/IL-1b/IL-6/PGE2-treated DCs (sDCs) supplemented with IP-10 produced strong cytotoxic T cells expressing higher level of IFN-g. Tetramer assay showed that CCL21-treated DCs enhanced generation of antigen-specific CTLs. Taken together, our data suggest that mDCs pre-stimulated by chemokine CCL21 enhanced migratory capacity to secondary lymphoid organs and produced strong cytotoxic T cells via IP-10 signaling pathway. Disclosures: No relevant conflicts of interest to declare.

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