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Frequency and surface phenotype of human T lymphocytes producing interleukin 2. Analysis by limiting dilution and cell cloning.
No full textIn this study we have determined the frequency and distribution of interleukin 2 (IL2)-producing cells and their precursors (IL2-P) in the two major subsets of human T cells. The two subsets were identified on the basis of their reactivity (or lack thereof) with anti-T4 or anti-T8 monoclonal antibodies. T4+T8- and T4-T8+ cells were first isolated from peripheral blood T cell populations by positive or negative selection using the fluorescence-activated cell sorter, and then analyzed for total IL2-P and cytolytic T lymphocyte precursor (CTL-P) frequencies using a limiting dilution microculture system which allows clonal growth of every T cell. The results indicated that 50-60% of peripheral blood T cells consisted of IL2-P. In the T4+T8- subset (which represents 60-65% of all T cells) about 75% of the cells were IL2-P, whereas about 15% of T4-T8+ cells exhibited this functional potential. In contrast, about 3% and greater than 95% of T4+T8- and T4-T8+ cells, respectively, were CTL-P. Thus, these data provide direct evidence that there is no absolute correlation between the surface phenotype and the functional potential of human peripheral blood T cells. Moreover, it is evident from this frequency analysis that a significant proportion of T4-T8+ cells have a dual functional potential. IL2-P and CTL-P frequencies were also determined in T cell populations which had been activated in allogeneic mixed lymphocyte culture. The IL2-P frequencies in total T, T4+T8- and T4-T8+ MLC populations were 30, 45 and 10%, respectively. Comparative analysis of IL2 production and CTL activity at the clonal level confirmed that up to 20% of alloreactive CTL with the T4-T8+ surface phenotype were able to produce IL2 upon specific stimulation. This dual functional capacity was also observed among T4+T8- CTL
The dialogue between human natural killer cells and dendritic cells
No full textThe interaction of NK cells with dendritic cells (DCs) appears to play an important role in both innate and adaptive immune responses to pathogens. In peripheral inflamed tissues the simultaneous engagement of receptors for danger (e.g. Toll-like receptors), which are expressed by both NK cells and DCs, results in cell activation and the acquisition of functional properties necessary for controlling, and possibly rapidly eliminating, pathogens by innate effector mechanisms. Moreover, NK cells are needed to select the most appropriate DCs that display the functional properties suitable for subsequent T-cell priming. This NK-cell-mediated programming of DC maturation is modulated by cytokines released during the early stages of inflammatory responses (i.e. IL-12, IFN-gamma, IL-4). NK cells and DCs continue their interactions in secondary lymphoid organs where both cell types play a role in the control of T-cell priming
Unravelling natural killer cell function: triggering and inhibitory human NK receptors.
No full textNatural killer (NK) cells represent a highly specialized lymphoid population characterized by a potent cytolytic activity against tumor or virally infected cells. Their function is finely regulated by a series of inhibitory or activating receptors. The inhibitory receptors, specific for major histocompatibility complex (MHC) class I molecules, allow NK cells to discriminate between normal cells and cells that have lost the expression of MHC class I (e.g., tumor cells). The major receptors responsible for NK cell triggering are NKp46, NKp30, NKp44 and NKG2D. The NK-mediated lysis of tumor cells involves several such receptors, while killing of dendritic cells involves only NKp30. The target-cell ligands recognized by some receptors have been identified, but those to which major receptors bind are not yet known. Nevertheless, functional data suggest that they are primarily expressed on cells upon activation, proliferation or tumor transformation. Thus, the ability of NK cells to lyse target cells requires both the lack of surface MHC class I molecules and the expression of appropriate ligands that trigger NK receptors
Commentary: Regulated equilibrium between opposite signals: a general paradigm for T cell function?
No full textThe co-signaling receptors specific for the different members of the B7 molecular family are cell surface glycoproteins that are essential to modulate and tune the TCR-mediated activation of T lymphocytes. The common characteristic is that their function appears to be dependent on the engagement of TCR by antigenic peptides presented in the MHC context by antigen-presenting cells. Interestingly, co-signaling molecules can be distinguished into costimulators and co-inhibitors, the prototype being represented by CD28 and CTLA-4, respectively. In the case of costimulators, the co-signals integrate the signal originated from the TCR resulting in optimal T cell activation (two-signal model). In the case of co-inhibitors, the co-signals would moderate and/or switch off the Ag-dependent T cell activation, thus acting as negative regulators of immune responses. The growing number of novel co-signaling molecules has recently highlighted the need to integrate the two-signal model with the emerging data on the different co-inhibitory interactions. Thus, a model has been proposed based on the idea that the TCR signal alone cannot take a full decision on the nature of the functional outcome following an antigen-specific stimulation and that this final event is governed by the co-signaling molecules
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