Different cell types function as APCs to activate naive T cells or previously differentiated effector T cells (Fig. and Table 1). DCs are the only cell type capable of capturing antigens and migrating to secondary lymphoid organs and are, therefore, the most effective APCs for activating naive T cells and for initiating T-cell responses. Macrophages and B lymphocytes also function as APCs, but mostly for previously activated CD4+ helper T cells rather than for naive T cells. DCs, macrophages, and B lymphocytes express MHC-II molecules and are therefore capable of activating CD4+ T lymphocytes. For this reason, these three cell types have been called professional APCs; however, this term is sometimes used to refer only to DCs because of their unique role in naive T-cell activation.
Fig1. Functions of different antigen-presenting cells. The three major types of antigen-presenting cells for CD4+ T lymphocytes function to display antigens at different stages and in different types of immune responses. Note that effector T cells activate macrophages and B lymphocytes by production of cytokines and by expressing surface molecules; these will be described in later chapters. Dendritic cells also present antigen to naive CD8+ T cells (not shown), and all nucleated cells can present antigen to CD8+ effector T cells, which respond by killing the antigen-producing cells (not shown).
Table1. Properties and Functions of Antigen-Presenting Cells a
APCs display peptide-MHC complexes for recognition by T cells and also provide additional stimuli that are required for the full responses of the T cells. Antigen, which is peptide bound to an MHC molecule, provides the first signal to T cells through the TCR, and the additional stimuli that are required for T cell activation are sometimes called second signals. These second signals are more important for the activation of naive T cells than for the restimulation of previously activated effector and memory cells. The membrane-bound molecules of APCs that function together with antigens to stimulate T cells are called costimulators. APCs also secrete cytokines that play critical roles in the differentiation of naive T cells into effector cells.
The antigen-presenting function of APCs is enhanced by expo sure to microbial products. This is one reason that the immune system responds better to microbes than to harmless, nonmicrobial substances. DCs and macrophages express Toll-like receptors and other innate immune microbial sensors and respond to microbes by increasing the expression of MHC molecules and costimulators, by improving the efficiency of antigen processing to generate peptides that bind to MHC molecules, and by activating the APCs to produce cytokines, all of which help stimulate T-cell responses. In addition, DCs that are activated by microbes express chemokine receptors that facilitate their migration to sites where naive T cells are present.
APCs that present antigens to T cells also receive signals back from these lymphocytes that enhance the antigen- presenting function of the APCs. In particular, CD4+ T cells that are activated by antigen recognition and costimulation express surface molecules, notably one called CD40 ligand (CD154), which binds to CD40 on DCs and macrophages, and the T cells also secrete cytokines, such as interferon-γ (IFN-γ), that bind to their receptors on these APCs. The combination of CD40 signals and cytokines activates the APCs, resulting in increased ability to process and present antigens, increased expression of costimulators, and secretion of cytokines that activate the T cells. This bidirectional interaction between APCs displaying the antigen and T lymphocytes that recognize the antigen functions as a positive feedback loop that plays an important role in maximizing the immune response.
