Tumor-specific T cell recptor gene transfection promotes memory T cell differentiation in vitro / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate effect of tumor-specific T cell receptor gene transfection on memory T cell differentiation in vitro.</p><p><b>METHODS</b>TCRVbeta7.1 gene was transferred into peripheral blood mononuclear cells (PBMCs) obtained from healthy adults, and the expression of Vbeta7.1 was detected by flow cytometry before and after the transfection. Memory T cell differentiation was induced by stimulation with the hepatocarcinoma cell line BEL-7402 in vitro. The expression of surface molecules CD45RO, CD45RA and CCR7 was analyzed by flow cytometry to identify the phenotype and subsets of the memory T cells. Fluorescence-activated cell sorting was performed to detect the apoptosis of the tumor cells, and enzyme-linked immunoabsorbent assay was used to determine the production of interferon-gamma (IFN-gamma) for assessing the immune function of the memory T cells.</p><p><b>RESULTS</b>Flow cytometry showed that TCRVbeta7.1 gene was efficiently expressed after transfection. After stimulation by the tumor cells in vitro, the expression of CD45RO in TCRVbeta7.1 gene-modified T cells increased gradually, and analysis of the coexpression of CD45RA and CCR7 revealed that the effector memory T cells constituted the majority of the differentiated memory T cells. The apoptotic rate of the tumor cells induced by the T cells increased significantly with also obviously increased INF-gamma secretion in the memory T cells.</p><p><b>CONCLUSION</b>Tumor-specific TCRVbeta7.1 gene transfection can promote the differentiation of the memory T cells, the majority of which belongs to effector memory T cells that perform immune functions by inducing apoptosis and cytokine secretion.</p>

Fator de necrose tumoral alfa (TNF- a) e asma: metanálise é a saída? / Tumor Necrosis Factor alpha (TNF-a) and Asthma: 15 Meta-ana/ysis the on/y way out?

O Fator de Necrose Tumoral Alfa (TNF-a) tem sido observado de perto nos últimos quinze anos e o emprego de ferramentas de biologia molecular tornou possível a descrição dos vários polimorfismos presentes em seu promotor. Acredita-se que a presença destes polimorfismos possa desempenhar papel crucial na regulação das funções do gene, propiciando em algumas situações a produção diferencial da citocina que por sua vez desempenha papéis centrais nos mecanismos inflamatórios, base do processo patológico que leva à asma. Nesta revisão procuramos explicar os critérios mais recentes adotados na realização de metanálise dos estudos de associação molecular, sem perder de vista a limitação deste método matemático quando aplicado à epidemiologia molecular

T-cell receptor V alpha gene repertoire and clonal expansion in benzene-exposed workers / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To observe the distribution of TCR V alpha gene repertoire and clonal expansion in peripheral blood mononuclear cells from 9 donors and 16 workers exposed to benzene.</p><p><b>METHODS</b>Complementarity determining region 3 (CDR3) of TCR V alpha subfamily genes were amplified using RT-PCR. The PCR products were further analyzed by genescan to evaluate clonality of T cells.</p><p><b>RESULTS</b>Almost all of 29 V alpha subfamily could be detected in 9 donors. 1 approximately 11 V alpha subfamilies were identified in all but one of the workers studied. The most frequently expressed V alpha subfamily were V alpha 3, V alpha 12 and V alpha 19 (68.8%), V alpha 14 (56.3%), with a lower expression rate found in V alpha 5, V alpha 15, V alpha 16, V alpha 22, V alpha 23 and V alpha 24 (6.3%). Clonal expansion T cells in one or more V alpha subfamily were found in 12 out of all workers studied, including oligoclonal, oligoclonal trend and biclonal patterns. The frequency of clonal expansion T cells in V alpha 12, V alpha 14 and V alpha 19 subfamilies were higher than others.</p><p><b>CONCLUSION</b>Skewed distribution and clonal expansion of TCR V alpha subfamily T cells could be found in workers exposed to benzene. V alpha 12, V alpha 14 and V alpha 19 subfamilies may be highly sensitive to benzene exposed. This is the first report of clonal expansion TCR V alpha T cells in the benzene-exposed group. The bias pattern of TCR V alpha T cells may be due to the immune cytotoxicity from benzene. However, whether the oligoclonality in some V alpha subfamilies reflect the phenomenon of clone absence or may be a response clone to benzene-related impairment during exposed to benzene, remains an open question.</p>

Receptores de células T y complejo CD3 / T cell receptors and CD3 complex

Tanto las células T como las células B contactan con antígenos a través de moléculas especializadas presentes en su superficie. En las células T, se han descrito dos tipos de estructuras para interactuar con los antígenos, se trata de los TCR alfa-beta y TCR gamma-delta. El primero, es el que se distribuye más ampliamente en las células T periféricas y timocitos portadores de un receptor definido. Se trata de moléculas heterodiméricas compuestas de dos cadenas polipeptídicas unidas entre sí. En una célula se expresan miles de copias de un receptor cuyas especificidades epitópicas son idénticas, sin embargo, la presencia de un tipo de receptor excluye la del otro. Las células T pueden ser, independiente del receptor desplegado, CD8- CD4+ o CD8+ CD4-, cumpliendo, por lo tanto, funciones ayudadoras o citotóxicas, respectivamente. Ambos receptores para efectuar sus actividades requieren de la expresión de un complejo proteico llamado CD3, compuesto por 5 proteínas denominadas alfa, delta, épsilon, dseta y eta cuya misión, en presencia de interacción con el antígeno, es transducir señales a través de la membrana celular del linfocito. El receptor de la célula T reconoce al antígeno asociado a proteínas de la membrana plasmática, conocidas como moléculas de histocompatibilidad clase I o II, dependiendo si se trata de células no inmunológicamente comprometidas, o bien, células presentadoras de antígeno o linfocitos, respectivamente. La estrategia para generar diversidad en los TCR es similar a la utilizada para las inmunoglobulinas. Los genes que codifican para los TCR se generan por medio de recombinaciones somáticas de segmentos génicos durante la etapa germinal de las células T