Oral tolerance correlates with high levels of lymphocyte activity

Castro-Junior, Archimedes Barbosa; Horta, Bernardo Coelho; Gomes-Santos, Ana Cristina; Cunha, André Pires da; Steinberg, Raphael S.; Nascimento, Danielle S.; Faria, Ana Maria Caetano; Vaz, Nelson M.

doi:10.1016/j.cellimm.2012.12.004

Cited by 20 publications

(19 citation statements)

References 40 publications

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“…Interestingly, there were more cures seen in the groups that were given anti-CD25 Ab at the time of feeding only and fed tumour (75%) than in those given Ab at the time of feeding and fed PBS (60%). It may be that Ag loading with feeding and subsequent inactivation of Tregs giving rise to increased Teff numbers could have occurred and similar findings have been demonstrated elsewhere [21].…”

Section: Discussionsupporting

confidence: 78%

Oral Tolerance to Cancer Can Be Abrogated by T Regulatory Cell Inhibition

et al. 2014

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Oral administration of tumour cells induces an immune hypo-responsiveness known as oral tolerance. We have previously shown that oral tolerance to a cancer is tumour antigen specific, non-cross-reactive and confers a tumour growth advantage. We investigated the utilisation of regulatory T cell (Treg) depletion on oral tolerance to a cancer and its ability to control tumour growth. Balb/C mice were gavage fed homogenised tumour tissue – JBS fibrosarcoma (to induce oral tolerance to a cancer), or PBS as control. Growth of subcutaneous JBS tumours were measured; splenic tissue excised and flow cytometry used to quantify and compare systemic Tregs and T effector (Teff) cell populations. Prior to and/or following tumour feeding, mice were intraperitoneally administered anti-CD25, to inactivate systemic Tregs, or given isotype antibody as a control. Mice which were orally tolerised prior to subcutaneous tumour induction, displayed significantly higher systemic Treg levels (14% vs 6%) and faster tumour growth rates than controls (p<0.05). Complete regression of tumours were only seen after Treg inactivation and occurred in all groups - this was not inhibited by tumour feeding. The cure rates for Treg inactivation were 60% during tolerisation, 75% during tumour growth and 100% during inactivation for both tolerisation and tumour growth. Depletion of Tregs gave rise to an increased number of Teff cells. Treg depletion post-tolerisation and post-tumour induction led to the complete regression of all tumours on tumour bearing mice. Oral administration of tumour tissue, confers a tumour growth advantage and is accompanied by an increase in systemic Treg levels. The administration of anti-CD25 Ab decreased Treg numbers and caused an increase in Teffs. Most notably Treg cell inhibition overcame established oral tolerance with consequent tumor regression, especially relevant to foregut cancers where oral tolerance is likely to be induced by the shedding of tumour tissue into the gut.

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Section: Discussionsupporting

confidence: 78%

Oral Tolerance to Cancer Can Be Abrogated by T Regulatory Cell Inhibition

et al. 2014

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“…Indeed, it was demonstrated previously that small adipocytes are more sensitive to insulin [42], which could be one factor responsible for the low levels of glucose in sensitized mice after oral challenge. Another factor to be taken into account is that the allergic suppression achieved is an active process [43] that consumes energy, or ultimately glucose.…”

Section: Discussionmentioning

confidence: 99%

Prolonged ingestion of ovalbumin diet by sensitized mice improves the metabolic consequences induced by experimental food allergy

Batista¹,

Pereira²,

Noviello³

et al. 2014

Clinical and Experimental Immunology

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SummaryThe prevalence of food allergy is rising in the western world. Allergen restriction is the chosen treatment in this condition, but continuous ingestion of the antigen has shown positive results in clinical trials. In a previous study, we have shown several allergic and metabolic alterations after 7 days of ovalbumin (OVA) ingestion by sensitized mice. The aim of this study was to investigate whether prolonged ingestion of antigen by sensitized mice would reverse the metabolic consequences caused by experimental food allergy. For this, allergic and metabolic parameters were analysed after prolonged ingestion of an OVA diet by OVA-sensitized mice. As shown previously, after 7 days of OVA consumption, sensitized mice showed increased serum levels of anti-OVA immunoglobulin (Ig)E and IgG1, aversion to the antigen ingestion, marked body and adipose tissue weight loss, followed by adipose tissue inflammation and decreased serum levels of adipokines, glucose and triglycerides. However, after 14 days of oral challenge, sensitized mice showed an anti-OVA IgE level similar to the mice that were only sensitized, but the specific IgG1 did not change. With this prolonged ingestion of OVA, sensitized mice were protected from OVA-induced anaphylaxis when the antigen was given systemically at a dose of 2 mg/animal. Moreover, various parameters analysed were significantly ameliorated, including adipose tissue inflammation, body and adipose tissue loss, as well as serum levels of adipokines and triglycerides. Therefore, our data suggest that prolonged ingestion of OVA by sensitized mice results in an improvement of the metabolic consequences caused by experimental food allergy.

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“…IFN-γ, IL-2, IL-7 and IL-10) that was observed in oral secretions may be representative of oral tolerance [24]. The oral cavity is exposed to a vast array of environmental antigens such as food and airborne particulate matter.…”

Section: Discussionmentioning

confidence: 99%

Comparison of the immune microenvironment of the oral cavity and cervix in healthy women

et al. 2013

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Background Despite similar frequencies of exposure, the low prevalence of certain sexually transmitted infections such as Chlamydia, HPV and HIV-1 in the oral cavity relative to the cervix is poorly understood. This could be explained in part by differences in host immune microenvironments between these two anatomic sites. Objective We compared the concentration and correlation of 27 different immune markers in paired secretion specimens collected from the oral and cervical mucosa of healthy women. Methods Paired oral and cervical secretion specimens were collected from thirty-nine women. The concentration of twenty-seven different immune markers was estimated using a Luminex multiplex assay. Marker concentration was normalized to total protein present in the specimen. Median immune marker concentrations were compared across anatomic sites. Unsupervised hierarchical clustering analysis was utilized to identify groups of markers that shared similar patterns of relative concentrations across anatomic sites. Results The oral cavity had significantly higher concentrations of eotaxin, IFN-γ, IL-2, IL-4, IL-5, IL-7, IL-9, IL-13, IL-15, PDGF-BB, TNF-α, (p < 0.01 for each) while the cervix had higher concentrations of proinflammatory markers such as FGF-basic, IL-1ra, IL-1β, IL-6, IL-8, IP-10, G-CSF, GM-CSF, MCP-1, MIP-1β, VEGF (p < 0.01 for each). Hierarchical cluster analysis identified two groups of immune markers comprised of T-cell related immune markers with significantly higher concentrations in the oral cavity relative to the cervix, and a third cluster consisting of mostly inflammatory immune markers which were higher concentrations in the cervix. The oral cavity had a larger number of significant inter-marker correlations as compared to the cervix. Conclusions The oral cavity and cervix have significantly different immune marker profiles, which may in part explain the significantly lower burden of sexually transmitted infections such as Chlamydia, HPV, and HIV-1 in the oral cavity vs. the cervix.

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Oral tolerance correlates with high levels of lymphocyte activity

Cited by 20 publications

References 40 publications

Oral Tolerance to Cancer Can Be Abrogated by T Regulatory Cell Inhibition

Oral Tolerance to Cancer Can Be Abrogated by T Regulatory Cell Inhibition

Prolonged ingestion of ovalbumin diet by sensitized mice improves the metabolic consequences induced by experimental food allergy

Comparison of the immune microenvironment of the oral cavity and cervix in healthy women

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