The instructive role of dendritic cells on T-cell responses

Abstract

Immune responses are initiated in the T-cell areas of secondary lymphoid organs where naïve T lymphocytes encounter dendritic cells (DCs) that present antigens taken up in peripheral tissues. DCs represent the interface between the universe of foreign and tissue-specific antigens and T lymphocytes, and they are the key players in the regulation of cell-mediated immunity. We discuss how the nature of the DC maturation stimuli and the density and quality of DCs present in the T-cell areas of secondary lymphoid organs determine the magnitude and class of the T-cell response.

Figure 1

Stochastic stimulation of proliferating T cells leads to intraclonal functional diversification. By establishing immunological synapses with dendritic cells (DCs), naïve T cells (green) achieve stimulation and become committed to proliferate in response to autocrine or paracrine IL-2. T-cell receptor stimulation is sustained by serial encounters with DCs and, in the presence of polarizing cytokines (IL-12 and IL-4, not shown), drives T-cell differentiation to Th1 or Th2 effector cells that have lost CCR7 expression (red). T cells receiving a shorter stimulation do not acquire effector function and do retain lymph-node homing capacity (yellow). An excessive stimulation leads to activation-induced cell death (black).

Figure 2

The maturation programme studied in monocyte-derived dendritic cells. DC, dendritic cells; ELC, endothelial-like cells; FcR, receptors for crystallizable fragment [of antibody]; GM-CSF, granulocyte/macrophage-colony-stimulating factor; ICAM-1, intracellular adhesion molecule-1; LPS, lipopolysaccharide; MIP, macrophage inflammatory protein; TARC, thymus- and activation-regulated chemokine.

Figure 3

Reactivity, flexibility, kinetics and exhaustion in myeloid and plasmacytoid dendritic cells (DCs). The figure summarizes the properties of immature myeloid and plasmacytoid DCs. Indicated are the most relevant Toll-like receptors (TLR) and chemokine receptors, and the response to various maturation stimuli. DC1 and DC2 refer to the capacity of the cells to induce Th1 and Th2 responses, respectively. CD40L, CD40 ligand; LPS, lipopolysaccharide; PGE2, prostaglandin E₂.