CCL19 (ELC) as an adjuvant for DNA vaccination: induction of a TH1-type T-cell response and enhancement of antitumor immunity

Westermann, Jörg; Nguyen-Hoai, Tam; Baldenhofer, Gerd; Höpken, Uta E.; Lipp, Martin; Dörken, Bernd; Pezzutto, Antonio

doi:10.1038/sj.cgt.7701042

Cited by 30 publications

(29 citation statements)

References 32 publications

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“…Previously, we reported that PBMCs from RRP patients respond to HPV proteins with increased expression of T H 2-like and regulatory cytokines without adequate expression of IFN-γ (8 to influenza virus (17). Additionally, CCL19 and CCL21 have been used as adjuvants to enhance CTL responses to tumors (20). Consistent with this, papillomas do not contain significant numbers of CTLs (9).…”

Section: Discussionsupporting

confidence: 60%

Immune Dysregulation and Tumor-Associated Gene Changes in Recurrent Respiratory Papillomatosis: A Paired Microarray Analysis

DeVoti

Rosenthal

et al. 2008

Mol Med

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Recurrent respiratory papillomas (RRP) are benign airway tumors, caused primarily by human papillomaviruses (HPV) types 6 and 11. The disease is characterized by multiple recurrences after surgical removal, with limited effective therapy. To identify novel targets for future therapy, we established transcriptional profiles for actively growing papillomas compared with autologous, clinically normal, laryngeal epithelia (adjacent tissue). Total ribonucleic acid (RNA) from 12 papillomas and 12 adjacent tissues were analyzed by microarray, and the matched sets of tissues compared by paired t test, to identify differentially expressed genes in papilloma tissues while minimizing variations intrinsic to individual patients. Quantitative polymerase chain reaction (PCR) was used to confirm the relative expression levels for a subset of genes. Within the 109 differentially expressed transcripts whose expression varied at least three-fold were two large groups of genes with related functions. The first group consisted of 18 genes related to host defense, including both innate and adaptive immunity. The second group contained 37 genes that likely contribute to growth of papillomas as benign tumors, since the altered pattern of expression also had been reported previously in many cancers. Our results support our previous studies that document a systemic T H 2-like adaptive immune response in RRP, and suggest that there is a role for altered innate immunity in RRP as well. We propose that HPV 6 and 11 infection establishes a tumorigenic microenvironment characterized by alteration of both innate inflammatory signals and adaptive immune responses that prevent effective T H 1-like response, in conjunction with altered expression of numerous genes that regulate cellular growth and differentiation.

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Section: Discussionsupporting

confidence: 60%

Immune Dysregulation and Tumor-Associated Gene Changes in Recurrent Respiratory Papillomatosis: A Paired Microarray Analysis

DeVoti

Rosenthal

et al. 2008

Mol Med

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“…CCL19 can directly affect immune responses of T cells and dendritic cells by skewing them towards a proinflammatory (Th1) response 48 49. However, CCL19 may have roles that depend on the species, as many of the CCL19 effects on Th1 skewing have been found in mice, some studies using CCL19/CCL21-deficient mice.…”

Section: Discussionmentioning

confidence: 99%

Global chemokine expression in systemic sclerosis (SSc): CCL19 expression correlates with vascular inflammation in SSc skin

et al. 2013

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Objective To characterise global chemokine expression in systemic sclerosis (SSc) skin in order to better understand the relationship between chemokine expression and vascular inflammation in this disease. Methods We investigated chemokine mRNA expression in the skin through quantitative PCR analysis comparing patients with diffuse cutaneous (dcSSc) or limited cutaneous (lcSSc) disease with healthy controls. We tested correlations between the most regulated chemokines and vascular inflammation and macrophage recruitment. CCL19 expression was examined in human primary immune cells treated with innate immune activators. Results The chemokines, CCL18, CCL19 and CXCL13, were upregulated in dcSSc skin, and CCL18 in lcSSc skin. Expression of CCL19 in dcSSc skin correlated with markers of vascular inflammation and macrophage recruitment. Immunofluorescence data showed CCL19 colocalisation with CD163 macrophages in dcSSc skin. In vitro studies on human primary cells demonstrated that CCL19 expression was induced after toll-like receptor activation of peripheral blood mononuclear cells and separated populations of CD14 monocytes. Conclusions CCL18, CCL19 and CXCL13—chemoattractants for macrophage and T cell recruitment—were three of six chemokines with the highest expression in dcSSc skin. Increased CCL19 expression in the skin suggests a role for CCL19 in the recruitment of immune cells to the peripheral tissue. Induction of CCL19 in macrophages but not structural cells indicates a role for skin-resident or recruited immune cells in perivascular inflammation. This study demonstrates that CCL19 is a sensitive marker for the perivascular inflammation and immune cell recruitment seen in dcSSc skin disease.

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“…CCR7 is also expressed on activated B cells and DCs, increasing the chance of interactions between DCs, T cells, and B cells in secondary lymphatic tissue. Previous studies demonstrated that CCL19 promotes antitumor activity (44,45) and enhances protective immune responses against HSV-1 (40).…”

mentioning

confidence: 99%

CCL19 and CCL28 Augment Mucosal and Systemic Immune Responses to HIV-1 gp140 by Mobilizing Responsive Immunocytes into Secondary Lymph Nodes and Mucosal Tissue

Luo

Tong

et al. 2013

The Journal of Immunology

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Induction of broad and potent neutralizing Abs at the mucosal portals of entry remains a primary goal for most vaccines against mucosally acquired viral infections. Selection of appropriate adjuvants capable of promoting both systemic and mucosal responses will be crucial for the development of effective immunization strategies. In this study, we investigated whether plasmid codelivery of cytokines APRIL, CCL19, or CCL28 can enhance Ag-induced immune responses to HIV-1 gp140. Our results demonstrated that pCCL19 and pCCL28, but not pAPRIL, significantly enhanced Ag-specific systemic and mucosal Ab responses. gp140-specific Abs in serum enhanced by pCCL19 or pCCL28 were broadly distributed across all four IgG subclasses, of which IgG1 was predominant. The enhanced systemic and mucosal Abs showed increased neutralizing activity against both homologous and heterologous HIV-1, and potency correlated with gp140-specific serum IgG and vaginal IgA levels. Measurement of gp140-specific cytokines produced by splenocytes demonstrated that pCCL19 and pCCL28 augmented balanced Th1/Th2 responses. pCCL19 and pCCL28 also increased IgA+ cells in colorectal mucosal tissue. pCCL19 codelivery resulted in an increase of CCR7+ CD11c+ cells in mesenteric lymph nodes and both CCR7+ CD11c+ cells and CCR7+ CD3e+ cells in spleen, whereas pCCL28 codelivery resulted in an augment of CCR10+ CD19+ cells in both spleen and mesenteric lymph nodes. Together, our data indicate that pCCL19 and pCCL28 can enhance HIV-1 envelope–specific systemic and mucosal Ab responses, as well as T cell responses. Such enhancements appear to be associated with mobilization of responsive immunocytes into secondary lymphoid organs and mucosal tissues through interactions with corresponding receptors.

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CCL19 (ELC) as an adjuvant for DNA vaccination: induction of a TH1-type T-cell response and enhancement of antitumor immunity

Cited by 30 publications

References 32 publications

Immune Dysregulation and Tumor-Associated Gene Changes in Recurrent Respiratory Papillomatosis: A Paired Microarray Analysis

Immune Dysregulation and Tumor-Associated Gene Changes in Recurrent Respiratory Papillomatosis: A Paired Microarray Analysis

Global chemokine expression in systemic sclerosis (SSc): CCL19 expression correlates with vascular inflammation in SSc skin

CCL19 and CCL28 Augment Mucosal and Systemic Immune Responses to HIV-1 gp140 by Mobilizing Responsive Immunocytes into Secondary Lymph Nodes and Mucosal Tissue

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