Development of antigen-specific T cells in mediastinal lymph nodes after intranasal immunization

Vendetti, Silvia; Riccomi, Antonella; Negri, Donatella; Veglia, Filippo; Sciaraffia, Ester; Magistris, Maria Teresa De

doi:10.1016/j.ymeth.2009.04.018

Cited by 7 publications

(10 citation statements)

References 29 publications

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“…Although early DC antigen presenting activity in the draining CLN was described for i. n. immunization experiments with viral antigens [28], our adjuvant candidate c-di-AMP alone did not notably induce T cell stimulatory molecules on APCs of the CLN after 24 h. The more pronounced DC activation was observed in the NALT, the lymphoid tissue directly associated with the site of administration, and also in the MLN. The early DC response in the MLN is in line with several studies reporting a similar observation upon i. n. immunization with model antigens and adjuvants [29]–[31] as well as upon i. n. infection with influenza virus [32]. We also demonstrated that murine DCs and MΦs/monocytes/granulocytes respond to in vivo administration of c-di-AMP by the up-regulation of IFN-β expression (Figure 4A).…”

Section: Discussionsupporting

confidence: 91%

The Mucosal Adjuvant Cyclic di-AMP Exerts Immune Stimulatory Effects on Dendritic Cells and Macrophages

et al. 2014

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The cyclic di-nucleotide bis-(3′,5′)-cyclic dimeric adenosine monophosphate (c-di-AMP) is a candidate mucosal adjuvant with proven efficacy in preclinical models. It was shown to promote specific humoral and cellular immune responses following mucosal administration. To date, there is only fragmentary knowledge on the cellular and molecular mode of action of c-di-AMP. Here, we report on the identification of dendritic cells and macrophages as target cells of c-di-AMP. We show that c-di-AMP induces the cell surface up-regulation of T cell co-stimulatory molecules as well as the production of interferon-β. Those responses were characterized by in vitro experiments with murine and human immune cells and in vivo studies in mice. Analyses of dendritic cell subsets revealed conventional dendritic cells as principal responders to stimulation by c-di-AMP. We discuss the impact of the reported antigen presenting cell activation on the previously observed adjuvant effects of c-di-AMP in mouse immunization studies.

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Section: Discussionsupporting

confidence: 91%

The Mucosal Adjuvant Cyclic di-AMP Exerts Immune Stimulatory Effects on Dendritic Cells and Macrophages

et al. 2014

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“…After four and five immunizations, the IgG titers of serum TT‐specific IgG were comparable in depleted and non‐depleted mice (data not shown). However, after five immunizations, when anti‐TT IgA can be detected at appreciable levels in the mucosal compartments, 17 the titers of mucosal anti‐TT‐specific IgA antibodies (vaginal washes and saliva) were still significantly lower in depleted as compared with non‐depleted mice (Figures 1e and f). These data indicate that ablation of CD25 + cells impairs the adjuvant activity of CT rather than enhancing it, suggesting that CD4 + CD25 + T cells are required for the adjuvant activity of CT.…”

Section: Resultsmentioning

confidence: 99%

“…The efficacy of vaccines can be greatly improved by adjuvants that enhance and modify the magnitude and the duration of the protective immunity. The bacterial toxin, cholera toxin (CT), is extraordinarily effective as a mucosal and systemic adjuvant, when it is co‐administered with Ag at mucosal sites 17 . CT mainly induces a Th2 immune response leading to an increase in Ag‐specific systemic and mucosal antibodies.…”

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confidence: 99%

Polyclonal Treg cells enhance the activity of a mucosal adjuvant

et al. 2010

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The efficacy of vaccines can be greatly improved by adjuvants that enhance and modify the magnitude and the duration of the immune response. Several approaches to design rational adjuvants are based on the suppression of regulatory T-cell (Treg) function. Here, we evaluated whether removal or addition of Treg at the time of vaccination with tetanus toxoid and the mucosal adjuvant cholera toxin (CT), would affect immune responses. We found that depletion/inactivation of CD4 + CD25 + Treg, either by treatment of BALB/c mice with anti-CD25 monoclonal antibodies or by adoptive transfer of CD4 + CD25 À T lymphocytes depleted of CD4 + CD25 + Treg into nu/nu mice, impaired antibody production after mucosal immunization in the presence of CT. Conversely, transfer of polyclonal, but not Ag-specific, CD4 + CD25 + Foxp3 + Treg to normal BALB/c mice enhanced CT-induced antibody responses. An increased titer of both immunoglobulin IgG1 and IgG2a antibody subclasses was found, however, the ratio between IgG1/IgG2a with or without polyclonal Treg was comparable, suggesting that polyclonal Treg influence the magnitude, but not the quality of the immune response. Recipients of polyclonal Treg that had been immunized with CT had an increased number of Ag-specific CD4 + T cells with an activated phenotype (CD44 hi ) in the draining lymph nodes. This accumulation of Ag-specific CD4 + T lymphocytes could favour the germinal centre formation and may promote T-dependent B-cell responses. Overall, our study indicates that Foxp3 + Treg can not only function as suppressor cells but also as helper T cells, depending on the type of immune response being evaluated and the microenvironment in which the response is generated.

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“…The OVA-specific clonal expansion was assessed in draining and distal lymph nodes 5 days after nasal immunization, since we previously demonstrated the presence of proliferated T cells within non draining sites at this time point [15], [16]. Mice nasally immunized with OVA and CpG ODN in the absence of FTY720 showed an Ag-specific clonal expansion of both CD4 + and CD8 + TgN cells in cervical and mediastinal lymph nodes that act as draining lymph nodes following intranasal immunization [21], and also in distal iliac and mesenteric lymph nodes, and in the spleen (Fig. 2 A and B).…”

Section: Resultsmentioning

confidence: 99%

Distribution of Primed T Cells and Antigen-Loaded Antigen Presenting Cells Following Intranasal Immunization in Mice

et al. 2011

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Priming of T cells is a key event in vaccination, since it bears a decisive influence on the type and magnitude of the immune response. T-cell priming after mucosal immunization via the nasal route was studied by investigating the distribution of antigen-loaded antigen presenting cells (APCs) and primed antigen-specific T cells. Nasal immunization studies were conducted using the model protein antigen ovalbumin (OVA) plus CpG oligodeoxynucleotide adjuvant. Trafficking of antigen-specific primed T cells was analyzed in vivo after adoptive transfer of OVA-specific transgenic T cells in the presence or absence of fingolimod, a drug that causes lymphocytes sequestration within lymph nodes. Antigen-loaded APCs were observed in mediastinal lymph nodes, draining the respiratory tract, but not in distal lymph nodes. Antigen-specific proliferating T cells were first observed within draining lymph nodes, and later in distal iliac and mesenteric lymph nodes and in the spleen. The presence at distal sites was due to migration of locally primed T cells as shown by fingolimod treatment that caused a drastic reduction of proliferated T cells in non-draining lymph nodes and an accumulation of extensively divided T cells within draining lymph nodes. Homing of nasally primed T cells in distal iliac lymph nodes was CD62L-dependent, while entry into mesenteric lymph nodes depended on both CD62L and α4β7, as shown by in vivo antibody-mediated inhibition of T-cell trafficking. These data, elucidating the trafficking of antigen-specific primed T cells to non-draining peripheral and mucosa-associated lymph nodes following nasal immunization, provide relevant insights for the design of vaccination strategies based on mucosal priming.

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Development of antigen-specific T cells in mediastinal lymph nodes after intranasal immunization

Cited by 7 publications

References 29 publications

The Mucosal Adjuvant Cyclic di-AMP Exerts Immune Stimulatory Effects on Dendritic Cells and Macrophages

The Mucosal Adjuvant Cyclic di-AMP Exerts Immune Stimulatory Effects on Dendritic Cells and Macrophages

Polyclonal Treg cells enhance the activity of a mucosal adjuvant

Distribution of Primed T Cells and Antigen-Loaded Antigen Presenting Cells Following Intranasal Immunization in Mice

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