In vivo activation of antigen-specific CD4 T cells

Physical detection of antigen-specific CD4 T cells has revealed features of the in vivo immune response that were not appreciated from in vitro studie s. In vivo, antigen is initially presented to naive CD4 T cells exclusively by dendritic cells within the T cell areas of secondary lymphoid tissues. Anatomic constraints make it likely that these dendritic cells acquire the antigen at the site where it enters the body. Inflammation enhances in vivo T cell activation by stimulating dendritic cells to migrate to the T cell areas and display stable peptide-MHC complexes and costimulatory ligands. O nce stimulated by a dendritic cell, antigen-specific CD4 T cells produce IL -2 but proliferate in an IL-2-independent fashion. Inflammatory signals ind uce chemokine receptors on activated T cells that direct their migration in to the B cell areas to interact with antigen-specific B cells. Most of the activated T cells then die within the lymphoid tissues. However, in the pre sence of inflammation, a population of memory T cells survives. This popula tion is composed of two functional classes. One recirculates through nonlym phoid tissues and is capable of immediate effector lymphokine production. T he other recirculates through lymph nodes and quickly acquires the capacity to produce effector lymphokines if stimulated. Therefore, antigenic stimul ation in the presence of inflammation produces an increased number of speci fic T cells capable of producing effector lymphokines throughout the body.