Células T reguladoras no linfoma cutâneo canino
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Data
2017-02-03
Autores
Semolin, Livia Maria Souza [UNESP]
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Editor
Universidade Estadual Paulista (Unesp)
Resumo
O linfoma pode ser caracterizado pela proliferação clonal de linfócitos malignos nos órgãos linfóides, podendo, porém, atingir diversos tecidos entre os quais a pele, denominado linfoma cutâneo. No cão, o linfoma cutâneo pode apresentar-se clinicamente por lesões localizadas ou generalizadas, podendo evoluir para lesões em placas e nódulos, muitas vezes edemaciados, ulcerados e hemorrágicos. Segundo avaliação histopatológica, podem ser classificados em epiteliotrópico ou não epiteliotrópico, com linhagem imunofenotípica T ou B, sendo o T mais comum. Células T reguladoras são linfócitos com capacidade imunossupressora, com papel importante na manutenção de processos fisiológicos, impedindo respostas de autoimunidade. Além disto, estudos demonstraram a influência das mesmas na supressão de respostas anti-tumorais, permitindo o escape das células neoplásicas dos mecanismos de defesa. Desta forma, o presente estudo teve como objetivo avaliar a presença das células T reguladoras em 12 cães com linfoma cutâneo T e 12 animais saudáveis, no sangue periférico e pele, através das técnicas de citometria de fluxo, avaliando porcentagens de Tregs, células T CD4+ e CD8+, e imuno-histoquímica, com a expressão tecidual de Foxp3. Observou-se maior número de Tregs no sangue periférico de cães com linfoma cutâneo (10,84±1,18) em relação aos animais saudáveis (5,67±0,89), sem diferença quanto às porcentagens de células CD4+ (48,26±4,54; 51,01±4,92, respectivamente) e CD8+ (30,32±4,82; 31,78±5,65, respectivamente). Não houve diferença nos valores celulares entre os animais com linfoma epiteliotrópico e não epiteliotrópico. Quanto à expressão tecidual de Foxp3 não foram observadas células imunomarcadas nos fragmentos cutâneos saudáveis, apenas nos linfomas cutâneos, com média de 8% (±5) de células positivas, demonstrando a presença de Tregs no tecido neoplásico, sem diferença entre os tipos histopatológicos. Não foi observada associação entre o número de Tregs e relação Treg/CD8, com a sobrevida dos pacientes. Não houve correlação entre os valores teciduais e sanguíneos das células T regulatoras nos animais com linfoma cutâneo. Desta forma, pode-se concluir que há estímulo para diferenciação e/ou proliferação de Tregs no ambiente tumoral de cães com linfoma cutâneo e aumento das mesmas na circulação, porém, não foi possível estabelecer exato valor prognóstico destas células.
Lymphoma can be characterized by clonal proliferation of malignant lymphocytes in the lymphoid organs, but may reach several tissues including the skin, called cutaneous lymphoma. In dogs, the cutaneous lymphoma may present clinically as localized or generalized lesions, wich may progress to plaque and nodules, often swollen, ulcerated and bleeding. Histologically, they can be classified as epitheliotropic or non-epitheliotropic, with immunophenotypic line T or B. Regulatory T cells are lymphocytes with immunosuppressive capacity, with a significant role in the maintenance of physiological processes, preventing autoimmunity responses. Furthermore, studies have demonstrated their influence in the suppression of anti-tumor responses, allowing the escape of neoplastic cells from the defense mechanisms. Thus, the present study aimed to evaluate the presence of regulatory T cells in 12 dogs with cutaneous T cell lymphoma and 12 healthy animals in peripheral blood and skin, through flow cytometry techniques, assessing blood concentration of Tregs, CD4+ and CD8+ , and immunohistochemical, through tissue expression of Foxp3. A higher number of Tregs in the peripheral blood of dogs with cutaneous lymphoma (10,84±1,18) was observed in relation to the healthy animals (5,67±0,89), with no difference in the percentages of CD4 + (48,26±4,54; 51,01±4,92, respectively) and CD8 + (30,32±4,82; 31,78±5,65, respectively) cells. There was no difference in cellular values between the animals with epitheliotropic and nonepitheliotropic lymphoma. Regarding the tissue expression of Foxp3, we did not observe marked cells in healthy cutaneous fragments, only in cutaneous lymphomas (8%+5), demonstrating the presence of Tregs in the neoplastic tissue, with no difference between histopathological types. No association was observed between the number of Tregs and the Treg/CD8 ratio, with the patients' survival. There was no correlation between tissue and blood values of regulatory T cells in animals with cutaneous lymphoma. In this way, it can be concluded that there is stimulus for differentiation and / or proliferation of Tregs in the tumor environment of dogs with cutaneous lymphoma, leading to their accumulation in the neoplastic tissue and consequently increase in circulation, but it was not possible to establish an exact value prognosis.
Lymphoma can be characterized by clonal proliferation of malignant lymphocytes in the lymphoid organs, but may reach several tissues including the skin, called cutaneous lymphoma. In dogs, the cutaneous lymphoma may present clinically as localized or generalized lesions, wich may progress to plaque and nodules, often swollen, ulcerated and bleeding. Histologically, they can be classified as epitheliotropic or non-epitheliotropic, with immunophenotypic line T or B. Regulatory T cells are lymphocytes with immunosuppressive capacity, with a significant role in the maintenance of physiological processes, preventing autoimmunity responses. Furthermore, studies have demonstrated their influence in the suppression of anti-tumor responses, allowing the escape of neoplastic cells from the defense mechanisms. Thus, the present study aimed to evaluate the presence of regulatory T cells in 12 dogs with cutaneous T cell lymphoma and 12 healthy animals in peripheral blood and skin, through flow cytometry techniques, assessing blood concentration of Tregs, CD4+ and CD8+ , and immunohistochemical, through tissue expression of Foxp3. A higher number of Tregs in the peripheral blood of dogs with cutaneous lymphoma (10,84±1,18) was observed in relation to the healthy animals (5,67±0,89), with no difference in the percentages of CD4 + (48,26±4,54; 51,01±4,92, respectively) and CD8 + (30,32±4,82; 31,78±5,65, respectively) cells. There was no difference in cellular values between the animals with epitheliotropic and nonepitheliotropic lymphoma. Regarding the tissue expression of Foxp3, we did not observe marked cells in healthy cutaneous fragments, only in cutaneous lymphomas (8%+5), demonstrating the presence of Tregs in the neoplastic tissue, with no difference between histopathological types. No association was observed between the number of Tregs and the Treg/CD8 ratio, with the patients' survival. There was no correlation between tissue and blood values of regulatory T cells in animals with cutaneous lymphoma. In this way, it can be concluded that there is stimulus for differentiation and / or proliferation of Tregs in the tumor environment of dogs with cutaneous lymphoma, leading to their accumulation in the neoplastic tissue and consequently increase in circulation, but it was not possible to establish an exact value prognosis.
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Palavras-chave
Cão, Citometria de fluxo, Foxp3, Neoplasia, Treg