The activation of CD8+ T cells is stimulated by recognition of class I MHC–associated peptides and requires costimulation and helper T cells. CD8+ T cells function in much the same manner to kill infected cells and tumor cells, and their responses to microbial anti gens and tumor antigens are essentially similar. How ever, the responses of CD8+ T cells differ in several ways from responses of CD4+ T lymphocytes:

• The initiation of CD8+ T cell activation often requires cytosolic antigen from one cell (e.g., virus-infected or tumor cells) to be cross-presented by dendritic cells .

• The differentiation of naive CD8+ T cells into fully active cytotoxic T lymphocytes (CTLs) and memory cells may require the concomitant activation of CD4+ helper T cells (Fig. 1). When virus-infected or tumor cells are ingested by dendritic cells, the APCs may present viral or tumor antigens from the cytosol in complex with class I MHC molecules and from vesicles in complex with class II MHC molecules. Thus, both CD8+ T cells and CD4+ T cells specific for viral or tumor antigens are activated near one another. The CD4+ T cells may produce cytokines or membrane molecules that help to activate the CD8+ T cells. This requirement for helper T cells in CD8+ T cell responses is the likely explanation for the increased susceptibility to viral infections and cancers in patients infected with the human immunodeficiency virus (HIV), which kills CD4+ but not CD8+ T cells.

Fig1. Activation of CD8+ T cells. Antigen-presenting cells (APCs), principally dendritic cells, may ingest and present microbial antigens to CD8+ T cells (cross-presentation) and to CD4+ helper T cells. Sometimes, the APC may be infected and can directly present antigens (not shown). The helper T cells then produce cytokines that stimulate the expansion and differentiation of the CD8+ T cells. Helper cells also may activate APCs to make them potent stimulators of CD8+ T cells. CTLs, Cytotoxic T lymphocytes.