RESUMO
The C-type lectin-like receptor CD161 is expressed by lymphocytes found in human gut and liver, as well as blood, especially natural killer (NK) cells, T helper 17 (Th17) cells, and a population of unconventional T cells known as mucosal-associated invariant T (MAIT) cells. The association of high CD161 expression with innate T-cell populations including MAIT cells is established. Here we show that CD161 is also expressed, at intermediate levels, on a prominent subset of polyclonal CD8+ T cells, including antiviral populations that display a memory phenotype. These memory CD161(int)CD8+ T cells are enriched within the colon and express both CD103 and CD69, markers associated with tissue residence. Furthermore, this population was characterized by enhanced polyfunctionality, increased levels of cytotoxic mediators, and high expression of the transcription factors T-bet and eomesodermin (EOMES). Such populations were induced by novel vaccine strategies based on adenoviral vectors, currently in trial against hepatitis C virus. Thus, intermediate CD161 expression marks potent polyclonal, polyfunctional tissue-homing CD8+ T-cell populations in humans. As induction of such responses represents a major aim of T-cell prophylactic and therapeutic vaccines in viral disease and cancer, analysis of these populations could be of value in the future.
Assuntos
Linfócitos T CD8-Positivos/imunologia , Colite Ulcerativa/imunologia , Doença de Crohn/imunologia , Memória Imunológica , Mucosa Intestinal/imunologia , Subfamília B de Receptores Semelhantes a Lectina de Células NK/imunologia , Células Th17/imunologia , Adenoviridae/imunologia , Antígenos CD/genética , Antígenos CD/imunologia , Antígenos de Diferenciação de Linfócitos T/genética , Antígenos de Diferenciação de Linfócitos T/imunologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/patologia , Ensaios Clínicos como Assunto , Colite Ulcerativa/genética , Colite Ulcerativa/patologia , Colo/imunologia , Colo/patologia , Doença de Crohn/genética , Doença de Crohn/patologia , Regulação da Expressão Gênica , Hepacivirus/imunologia , Hepatite C/imunologia , Hepatite C/prevenção & controle , Hepatite C/virologia , Humanos , Cadeias alfa de Integrinas/genética , Cadeias alfa de Integrinas/imunologia , Mucosa Intestinal/patologia , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/patologia , Lectinas Tipo C/genética , Lectinas Tipo C/imunologia , Ativação Linfocitária , Subfamília B de Receptores Semelhantes a Lectina de Células NK/genética , Cultura Primária de Células , Transdução de Sinais , Proteínas com Domínio T/genética , Proteínas com Domínio T/imunologia , Acetato de Tetradecanoilforbol/farmacologia , Células Th17/efeitos dos fármacos , Células Th17/patologiaRESUMO
Type 1 diabetes (T1D) is an autoimmune disease arising as a consequence of a misdirected T cell response to the pancreatic beta cell. In recent years, there has been a growing interest in the innate immune system as a regulator of disease development. Genome-wide association studies have identified diabetes-associated polymorphisms in genes encoding proteins with functions related to the innate immune response. Moreover, enteroviruses, known to activate a strong innate immune response, have been implicated in the disease pathogenesis. In this review, we discuss the innate immune response elicited by enteroviruses and how this response may regulate T1D development.
