RESUMO
Most models regarding the 'clonal' origin of CD8(+) T cell effector and memory subset diversification suggest that during the first contact of a naïve T cell with the priming antigen-presenting cell major decisions for subsequent differentiation are made. Data using novel single-cell T cell tracking technologies demonstrate that a single naïve CD8(+) T cell can give rise to virtually all different subtypes of effector and memory T cells, and direct major determinants of subset diversification to the time period beyond the first cell division. Thereby, some 'stem cell-like' characteristics typical for naïve T cells are probably still maintained within distinct subsets of memory T cells. These observations have direct consequences for clinical applications like adoptive T cell therapy.
Assuntos
Linfócitos T CD8-Positivos/metabolismo , Diferenciação Celular/imunologia , Citotoxicidade Imunológica , Memória Imunológica , Subpopulações de Linfócitos T/metabolismo , Animais , Biomarcadores/metabolismo , Linfócitos T CD8-Positivos/citologia , Linfócitos T CD8-Positivos/imunologia , Linhagem da Célula , Proliferação de Células , Homeostase/imunologia , Humanos , Imunoterapia Adotiva , Receptores de Antígenos de Linfócitos T/imunologia , Transdução de Sinais , Células-Tronco/imunologia , Células-Tronco/metabolismo , Subpopulações de Linfócitos T/citologia , Subpopulações de Linfócitos T/imunologiaRESUMO
In addition to their bridging function between innate and adaptive immunity, dendritic cells (DCs) may also contribute to primary resistance against infection. Here we analyzed the role of DCs during infection with Listeria monocytogenes by performing systemic in vivo depletion of these cells. We showed that CD8alpha(+) DCs were crucial for L. monocytogenes spreading and proliferation in the spleen. Efficient and rapid uptake of L. monocytogenes by CD8alpha(+) DCs required the small GTPase Rac1 and is a general characteristic of this DC subpopulation in filtering particles out of the blood. Thus, CD8alpha(+) DCs appear to play an important role for efficient bacterial entry into the spleen, which is of relevance for subsequent immune responses.
Assuntos
Antígenos CD8/análise , Células Dendríticas/imunologia , Listeria monocytogenes , Listeriose/imunologia , Baço/microbiologia , Animais , Antígeno CD11c/análise , Células Dendríticas/microbiologia , Células Dendríticas/transplante , Granulócitos/imunologia , Listeriose/enzimologia , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos , Neuropeptídeos/genética , Neuropeptídeos/metabolismo , Baço/citologia , Baço/imunologia , Linfócitos T/imunologia , Proteínas rac de Ligação ao GTP/genética , Proteínas rac de Ligação ao GTP/metabolismo , Proteínas rac1 de Ligação ao GTPRESUMO
The activating receptor NKG2D recognizes a wide range of different ligands, some of which are primarily expressed in "stressed" tissues or on tumor cells. Until now, similar stimulatory effects on natural killer and CD8+ T cells have been described for all NKG2D ligands, and the NKG2D receptor/ligand system has therefore been interpreted as a sensor system involved in tumor immune surveillance and activation of immune responses. We show here that the NKG2D ligands H60 and MIC class 1 chain-related protein A (MICA) can also mediate strong suppressive effects on T cell proliferation. Responsiveness to H60- and MICA-mediated suppression requires IL-10 and involves a receptor other than NKG2D. These findings might provide explanations for the observation that strong in vivo NKG2D ligand expression, such as that on tumor cells, sometimes fails to support effective immune responses and links this observation to a distinct subgroup of NKG2D ligands.