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Abstract Introduction: Oral tolerance is defined as the suppression of the immune response to antigens that have been previously administered orally. The purpose of inducing oral tolerance is to avoid using immunosuppressive drugs since, considering that they are not antigen-specific, they make the host more susceptible to acquire infections and develop neoplasms. Objective: To carry out a literature review on the most relevant theoretical references regarding oral tolerance induction in organ and tissue transplantation to prove that oral tolerance is a viable alternative therapy in transplant patients. Materials and methods: A literature review was conducted in the PubMed, MEDLINE, LILACS and Embase databases using the following search strategy: publication time: no limits; publication language: English and Spanish; type of studies: case-control studies, literature and systematic reviews; search terms: "T-Lymphocytes, Regulatory", "Autoimmunity", Immunosuppression", "Immune system" and "Immune Tolerance", and their equivalents in Spanish. Results: After the initial search was completed, 719 records were retrieved; however, only 99 addressed oral tolerance induction. Once duplicate records and articles without full-text access were removed, 75 studies were included for analysis. Conclusions: Oral administration of antigens is an effective way to induce immune tolerance in transplant patients (murine models) as it eliminates the adverse effects associated with immunosuppressive therapy, which currently is the standard therapy to treat these patients worldwide.

Resumen Introducción. La tolerancia oral es la supresión de la respuesta inmune a antígenos administrados con anterioridad por vía oral; su inducción tiene el propósito de evitar el uso de fármacos inmunosupresores, los cuales, dado que son poco específicos a antígenos, vuelven al huésped más susceptible de contraer infecciones y desarrollar neoplasias. Objetivos. Realizar una revisión de la literatura sobre los referentes teóricos más relevantes de la inducción de a tolerancia oral en lo que respecta al trasplante de órganos y tejidos para demostrar que el uso de esta alternativa terapéutica es viable en pacientes trasplantados. Materiales y métodos. Se realizó una revisión de la literatura en PubMed, MEDLINE, LILACS y Embase mediante la siguiente estrategia de búsqueda: periodo de publicación: sin límites; idiomas: Inglés y Español; tipo de artículos: estudios caso-control, revisiones sistemáticas y de la literatura; términos de búsqueda: "T-Lymphocytes, Regulatory", "Autoimmunity", Immunosuppression", "Immune system" and "Immune Tolerance", y sus equivalentes en español. Resultados. La búsqueda inicial arrojó 719 registros, sin embargo solo 99 abordaban la inducción de la tolerancia oral. Una vez los registros duplicados y los artículos sin acceso a texto completo fueron removidos, se incluyeron 72 estudios en la revisión. Conclusiones. La administración oral de antígenos es una opción efectiva para inducir tolerancia inmunológica en pacientes trasplantados (modelos murinos), pues elimina los efectos adversos que conlleva la terapia inmunosupresora actualmente utilizada.

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ABSTRACT Objective To analyze and compare the expression of Toll-like receptors by regulatory T cells present in the peritoneal fluid of patients with and without endometriosis. Methods Regulatory T cells were isolated from peritoneal fluid of women with and without endometriosis, collected during surgery, and mRNA was extracted for analysis of Toll-like receptors expression by reverse-transcriptase polymerase chain reaction. Results Patients with endometriosis presented regulatory T cells expressing a larger number and variety of Toll-like receptors when compared to regulatory T cells from patients in the Control Group. Toll-like receptor-1 and Toll-like receptor-2 in regulatory T cells were expressed in both groups. All other expressed Toll-like receptors types were only found in regulatory T cells from the Endometriosis Group. Conclusion Patients with endometriosis had peritoneal regulatory T cells expressing various Toll-like receptors types.

RESUMO Objetivo Analisar e comparar a expressão de receptores do tipo Toll por células T reguladoras presentes no líquido peritoneal de pacientes com endometriose. Métodos Células T reguladoras foram isoladas do líquido peritoneal de mulheres com e sem endometriose, coletadas durante a cirurgia, e o RNAm foi extraído para análise da expressão de receptores do tipo Toll por reação em cadeia da polimerase com transcriptase reversa. Resultados Pacientes com endometriose apresentaram células T reguladoras expressando maior número e variedade de Toll por células quando comparadas com T reguladoras de pacientes do Grupo Controle. Receptores do tipo Toll-1 e receptores do tipo Toll-2 foram expressos em ambos os grupos. Todos os outros tipos de receptores Toll foram encontrados expressos apenas em células T reguladoras do grupo com endometriose. Conclusão Pacientes com endometriose apresentaram células T reguladoras peritoneais expressando vários tipos de receptores tipo Toll.

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Abstract Regulatory T (Treg) cells can suppress antitumor immune response, but little is known about possible age-related differences in the number of these cells in the microenvironment of oral tongue squamous cell carcinoma (OTSCC). The aim of this study was to determine the number of FoxP3+ Treg cells in the microenvironment of OTSCC in young (≤ 45 years) and older (≥ 60 years) patients, and to correlate the findings with clinicopathological parameters (sex, tumor size/extent, regional lymph node metastasis, clinical staging, and histopathological grade of malignancy). Forty-eight OTSCCs (24 diagnosed in young patients and 24 diagnosed in older patients) were selected. Lymphocytes exhibiting nuclear immunopositivity for FoxP3 were quantified at the tumor invasive front and the results were analyzed statistically using the non-parametric Mann-Whitney test. FoxP3+ lymphocytes were observed in all cases assessed. The number of FoxP3+ lymphocytes in OTSCC tended to be higher in older patients (p = 0.055). Analysis of OTSCC in males and in early clinical stages revealed a higher number of Treg cells in older patients than in young ones (p < 0.05). In older patients, the number of Treg cells tended to be higher in smaller tumors (p = 0.079). Tumors with intense inflammatory infiltrate exhibited a larger number of Treg cells, both in young (p = 0.099) and older patients (p = 0.005). The results suggest a greater participation of Treg cells in immunoinflammatory responses in the microenvironment of OTSCC in older patients, particularly in males and in early stages.

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Abstract Cytokines and chemokines have a fundamental role in the maintenance of inflammation and bone response, which culminate in the development of chronic periapical lesions. Regulatory (Treg) and Th17 cytokines play a key role in regulating the immune response involved in this process. The aim of this study was to investigate the role of Treg and Th17 cells in chronic inflammatory periapical disease, by comparing the expression of the immunoregulatory mediators TGF-β, IL-10, CCL4, and the proinflammatory IL-17 and CCL20 in the periapical tissue of teeth with pulp necrosis, with and without associated chronic lesions. Eighty-six periapical tissue samples were obtained from human teeth. The samples were divided into three groups: pulp necrosis with a periapical lesion (n=26); pulp necrosis without a periapical lesion (n=30), and control (n=30). All samples were submitted to histopathological analysis and cytokine and chemokine measurement through ELISA. Statistical analyses were done with Kruskal-Wallis and Mann-Whitney tests and Spearman correlation. The group with pulp necrosis and a periapical lesion showed a higher expression of CCL4 and TGF-β in comparison with pulp necrosis without a lesion. CCL20 was higher in the group with a periapical lesion when compared to the control. In all groups there was a weak positive correlation between IL-17/CCL20, IL-10/CCL4, and IL-17/TGF-β. Both types of cytokines, pro-inflammatory and immunoregulatory, occur simultaneously in periapical tissue. However, a rise in immunosuppressive cytokines and chemokines (CCL4 and TGF-β) in periapical lesions suggests a role of these cytokines in stable periapical disease.

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Abstract: Human Leukocyte Antigen G (HLA-G) is a molecule involved in the tumor immunosuppression and also in the generation of regulatory T (Treg) cells, thus leading to evasion to the immune system host, and consequently, contributing to tumor progression in several cancers. The aim of this study was to evaluate the immunoexpression of HLA-G by tumor cells and FoxP3+ Treg cells in 25 oral tongue squamous cell carcinomas (SCCs) and 25 lower lip SCCs and analyze their relationship with clinical parameters. HLA-G expression was higher in oral tongue SCCs than in lower lip SCCs. In oral tongue SCCs and lower lip SCCs, no association between HLA-G expression and clinical parameters (tumor size, lymph node status, distant metastasis, and clinical stage) was verified (P>0.05). FoxP3+ Treg cells were detected along the tumor invasive front in all cases of oral tongue and lower lip SCCs. In oral tongue SCC cases, the number of Treg cells tended to be higher in smaller tumors, tumors without regional lymph node metastasis, and tumors in early clinical stages, but the difference was not statistically significant (P>0.05). A significant positive correlation was found between the expression of HLA-G by neoplastic cells and Treg cells in lower lip SCCs (p = 0.008). Our findings suggest the involvement of HLA-G and Treg cells in the modulation of immune responses in oral tongue and lower lip SCCs. This interaction between HLA-G and Treg cells may represent an evasion mechanism in these malignancies.

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Abstract: The aim of this study was to determine the number of FoxP3+ regulatory T (Treg) cells in the microenvironment of lower lip squamous cell carcinomas (LLSCCs) and to correlate the findings with clinicopathological parameters (tumor size/extent, regional lymph node metastasis, clinical stage, and histopathological grade of malignancy). Fifty cases of LLSCC were selected. Lymphocytes exhibiting nuclear immunostaining for FoxP3 were quantified in 10 microscopic fields at the deep invasive front of LLSCCs. The results were analyzed statistically using the nonparametric Mann-Whitney test and Fisher's exact test. FoxP3+ lymphocytes were observed in all cases studied. The number of these cells tended to be higher in smaller tumors, tumors without regional lymph node metastasis, and tumors in early clinical stages, but the difference was not statistically significant (p > 0.05). Low-grade tumors contained a larger number of FoxP3+ lymphocytes than high-grade tumors (p = 0.019). Tumors with an intense inflammatory infiltrate exhibited a larger number of Treg cells (p = 0.035). On the other hand, the number of FoxP3+ lymphocytes was smaller in tumors arranged in small cell clusters (p = 0.003). No significant differences in the number of FoxP3+ lymphocytes were observed according to the degree of keratinization (p = 0.525) or nuclear pleomorphism (p = 0.343). The results suggest the participation of Treg cells in immune and inflammatory responses in the microenvironment of LLSCCs. These cells may play a more important role in early stages rather than in advanced stages of lip carcinogenesis.

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Líquen plano (LP) é uma doença mucocutânea de natureza inflamatória crônica de etiologia ainda desconhecida. A estimulação da imunidade inata via os receptores Toll-like (TLRs) podem influenciar as células dendríticas e direcionar a resposta de células T CD4+ e CD8+ efetoras, assim como também favorecer o estado inflamatório do LP. OBJETIVOS: Avaliar o perfil fenotípico de células dendríticas mielóides (mDCs) e plasmocitóides (pDCs) e de linfócitos T CD4+ e CD8+ após estímulo com agonistas de TLRs no sangue periférico de pacientes com LP. Além disto, avaliar a frequência, perfil de maturação e os subtipos de células T CD4+ e TCD8+ reguladores. MÉTODOS: Foram selecionados 18 pacientes com LP (15 mulheres, 3 homens), com 41,57 ± 4,73 anos de idade e um grupo controle com 22 indivíduos sadios (18 mulheres, 4 homens), com 43,92 ± 7,83 anos de idade. As células mononucleares (CMNs) de sangue periférico foram avaliadas por citometria de fluxo quanto à: 1) Produção de TNF-? em mDCs e de IFN-? em pDCs em CMNs ativadas por agonistas de TLR 4, 7, 7/8 e 9; 2) Análise de células T CD4+ e CD8+ monofuncionais e polifuncionais após estímulo com agonistas de TLR 4, 7/8, 9 e enterotoxina B de Staphylococcus aureus (SEB); 3) Avaliação de células Th17 e Th22/Tc22 em CMNs após estímulo com SEB; 4) Frequência, perfil de maturação e subtipos de células T CD4+ e CD8+ reguladoras. RESULTADOS: 1) Nos pacientes com LP foi demonstrado um aumento na frequência de mDCs TNF-alfa+ após estímulo com agonistas de TLR4/LPS e TLR7-8/CL097, mas com imiquimode/TLR7 houve diminuição da expressão de CD83. Já nas pDCs do grupo LP, o imiquimode foi capaz de diminuir a expressão de CD80 e o CpG/TLR9 diminuiu a expressão de CD83 no LP. 2) As células T CD4+ secretoras de IL-10 mostraram aumento da frequência nos níveis basais, que diminuiu após estímulo com LPS e SEB. Em contraste, a produção de IFN-y aumentou em resposta ao LPS enquanto diminuiu para CpG. As células...

Lichen planus (LP) is a mucocutaneous disease of chronic inflammatory course of unknown etiology. Stimulation of the innate immune system via Toll-like receptors (TLRs) may influence the dendritic cells and targeting the CD4+ and effector CD8+ T cell responses, as well as promoting inflammatory status of the LP. OBJECTIVES: To evaluate the phenotypic profile of myeloid dendritic cells (mDCs), plasmacytoid (pDCs) and CD4+ and CD8+ T lymphocytes after stimulation with TLR agonists in peripheral blood of patients with LP. Moreover, to evaluate the frequency, maturation profile and subtypes of CD4+ and CD8+ T regulators cells. METHODS: We selected 18 patients with LP (15 women, 3 men) with 41.57 ± 4.73 years old and a control group of 22 healthy subjects (18 women, 4 men), with 43.92 ± 7, 83 years old. Mononuclear cells from peripheral blood (PBMCs) were assessed by flow cytometry for: 1) mDC TNF-alfa production and pDCs IFN-alfa production in PBMCs activated by agonists of TLR 4, 7, 7/8 and 9; 2) Analysis of monofunctional and polyfunctional CD4+ and CD8+ T cells after stimulation with TLR 4 agonists, 7/8, 9 and Staphylococcus aureus enterotoxin B (SEB); 3) Evaluation of Th17 and Th22/ Tc22 cells in PBMCs after stimulation with SEB; 4) Frequency, maturation profile and subtypes of regulatory CD4+ and CD8+ T cells. RESULTS: 1) Patients with LP showed an increased frequency of TNF-alfa+ mDCs after stimulation with agonists of TLR4/LPS and TLR7-8 /CL097, whereas with imiquimod /TLR7 induced a decreased CD83 expression. Already in the pDCs of LP group the imiquimod was able to decrease the CD80 expression and CpG/TLR9 decreased CD83 expression. 2) CD4+ T cells secreting IL-10 demonstrated an increased frequency at the baseline levels, which decreased after stimulation with LPS and SEB. In contrast, the production of IFN-y increased in response to LPS while decreased to CpG. Polyfunctional CD4+ T cells secreting simultaneously 5...

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BACKGROUND: Leprosy is characterized histologically by a spectrum of different granulomatous skin lesions, reflecting patients' immune responses to Mycobacterium leprae. Although CD4+CD25+ FoxP3+ T regulatory cells are pivotal in the immuneregulation, presence, frequency, and distribution of Tregs in leprosy, its reactional states have been investigated in few studies. OBJECTIVES: This study aimed to verify the frequency and distribution of regulatory T cells in different clinical forms and reactional states of leprosy. METHODS: We performed an immunohistochemical study on 96 leprosy cases [Indeterminate (I): 9 patients; tuberculoid tuberculoid: 13 patients; borderline tuberculoid: 26 patients; borderline borderline: 3 patients; borderline lepromatous: 8 patients; lepromatous lepromatous: 27 patients; reversal reaction: 8 patients; and erythema nodosum leprosum: 2 patients]. RESULTS: FoxP3-positive cells were present in 100% of the cases with an average density of 2.82% of the infiltrate. Their distribution was not related to granulomatous structures or special locations. There was a statistically significant increment of FoxP3 expression in patients with leprosy reversal reactions when compared with patients presenting with type I leprosy (P= 0.0228); borderline tuberculoid leprosy (P = 0.0351) and lepromatous leprosy (P = 0.0344). CONCLUSIONS: These findings suggest that Tregs play a relevant role in the etiopathogenesis of leprosy, mainly in type I leprosy reaction. .

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Introdução: A rinite alérgica (RA) é uma doença não infecciosa da mucosa nasal mediada por IgE após o contato com alérgenos. Objetivo: Investigar as células Th17 periféricas e CD4 + CD25 + Foxp3 + células T reguladoras (Treg) e a expressão sérica de citocinas em pacientes com RA. Métodos: De março a maio de 2012, foi coletado o sangue periférico de 14 pacientes com RA (grupo RA) e seis indivíduos saudáveis (grupo controle). A detecção das células Th17 e células Treg foi realizada através da citometria de fluxo e os níveis séricos de IL -17 e TGF- β1. Foram medidos por ELISA. Resultados: A percentagem de células Th17 no grupo RA foi bem maior do que no grupo controle (p < 0,01). A proporção de células Treg no grupo RA também foi drasticamente menor quando comparada ao grupo controle (p < 0,01). No grupo RA, o nível sérico de IL-17 foi significativamente maior do que no grupo controle (p < 0,01). Conclusão: O desequilíbrio de células Th17/Treg periféricas desempenha um papel importante na patogênese da RA. .

Introduction: Allergic rhinitis (AR) is an IgE-mediated non-infectious disease of the nasal mucosa following contact with allergens. Objective: To investigate the peripheral Th17 cells and CD4 + CD25 + Foxp3 + regulatory T (Treg) cells and the expression of cytokines in the serum of AR patients. Methods: The peripheral blood of 14 patients with AR (AR group) and six healthy subjects (control group) was collected from March to May of 2012. Flow cytometry was performed to detect the Th17 cells and Treg cells, and enzyme-linked immunosorbent assay (ELISA) to measure the serum levels of IL-17 and TGF-β1. Results: The proportion of Th17 cells in the AR group was markedly higher than that in the control group (p < 0.01). The proportion of Treg cells in the AR group was also dramatically reduced when compared with the control group (p < 0.01). In the AR group, serum IL-17 levels were markedly higher than those in the control group (p < 0.01). In the AR group, serum TGF-β1 levels were significantly lower than those in the control group (p < 0.01). Conclusion: The imbalance of peripheral Th17/Treg cells plays an important role in the pathogenesis of AR. .

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A infecção pelo Toxoplasma gondii é uma importante causa de doença ocular, tanto em indivíduos imunocomprometidos como em imunocompetentes. A patogênese da destruição retinocoroidiana associada a essa infecção ainda não está totalmente esclarecida. Nesta revisão, discute-se o papel do sistema imune no controle da infecção pelo Toxoplasma, especialmente, no olho.

Toxoplasma gondii infection is an important cause of ocular disease in both immunocompromised and immunocompetent subjects. The pathogenesis of retinochoroidal lesion associated with this infection is not fully understood. In this review, the role of the immune system in the control of Toxoplasma infection, especially in the eye, is discussed.

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