RESUMO
Themis (thymocyte-expressed molecule involved in selection), a member of a family of proteins with unknown functions, is highly conserved among vertebrates. Here we found that Themis had high expression in thymocytes between the pre-T cell antigen receptor (pre-TCR) and positive-selection checkpoints and low expression in mature T cells. Themis-deficient thymocytes showed defective positive selection, which resulted in fewer mature thymocytes. Negative selection was also impaired in Themis-deficient mice. A greater percentage of Themis-deficient T cells had CD4(+)CD25(+)Foxp3(+) regulatory and CD62L(lo)CD44(hi) memory phenotypes than did wild-type T cells. In support of the idea that Themis is involved in TCR signaling, this protein was phosphorylated quickly after TCR stimulation and was needed for optimal TCR-driven calcium mobilization and activation of the kinase Erk.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Diferenciação Celular/fisiologia , Linhagem da Célula/fisiologia , Proteínas/metabolismo , Sequência de Aminoácidos , Animais , Linfócitos T CD4-Positivos/citologia , Linfócitos T CD8-Positivos/citologia , Sobrevivência Celular/fisiologia , Células Cultivadas , Clonagem Molecular , Feminino , Citometria de Fluxo , Humanos , Peptídeos e Proteínas de Sinalização Intercelular , Camundongos , Camundongos Knockout , Dados de Sequência Molecular , Análise de Sequência com Séries de Oligonucleotídeos , Especificidade de Órgãos , Proteínas/genética , Receptores de Antígenos de Linfócitos T/metabolismo , Transdução de Sinais/fisiologiaRESUMO
The current literature suggests that cord blood (CB) cells are functionally immature. We previously reported that CB sera inhibit T cell proliferation and suggested that the microenvironment in which CB T cells reside may be, in part, responsible for their reduced function. In this study we have tried to explain some of the actions of the CB sera on peripheral blood mononuclear cells (PBMC). We showed that, as expected CB sera decreased the anti-CD3 and anti-CD28-induced proliferative response of PBMC (p < 0.01) but unexpectedly, increased the interleukin-2 (IL-2) specific proliferation of both a human T cell line (p < 0.005) and T cells within a mononuclear cell population (p < 0.05). These findings prompted us to analyse the effect of CB sera on the T cell ability to make and respond to IL-2. Stimulation of T cells in the presence of CB sera increased the frequency of IL-2 producing cells (p < 0.005) (but not the amount of IL-2 secreted) and resulted in a higher expression of CD25 (p < 0.05). Furthermore CB sera (in the presence and absence of IL-2) made the cells apoptose less (p < 0.005) than adult sera. Our results go some way to explaining the effect of the CB microenvironment on CB cellular function.