CD8(+) T cells: foot soldiers of the immune system

Abstract

Resting naive CD8(+) T cells have an astounding capacity to react to pathogens by massive expansion and differentiation into cytotoxic effector cells that migrate to all corners of the body to clear the infection. The initial interaction with antigen-presenting cells in the central lymphoid organs drives an orchestrated program of differentiation aimed at producing sufficient numbers of effectors to get the job done without resulting in clonal exhaustion. Interactions with antigen-presenting cells and other immune cells continue at the site of infection to regulate further on-site expansion and differentiation, all with the goal of protecting the host with minimal bystander tissue damage. Here we review recent advances in CD8(+) T cell recognition of antigen in lymphoid as well as in nonlymphoid tissues in the periphery, and how CD8(+) T cell expansion and differentiation are controlled in these contexts.

Figure 1

IL-2- and Blimp-1-Dependent Effector CD8⁺ T Cell Differentiation After antigen priming, activated CD8⁺ T cells receive signals from multiple cytokines such as IL-2, IL-21, Il-12, and Il-27. IL-2 signaling induces Blimp-1 expression which cooperates with other transcription factors to promote CD8⁺ (CTL) T cell effector differentiation, migration to the peripheral sites during acute infection, and exhaustion during chronic infection while inhibiting MPEC and Tcm cell differentiation.

Figure 2

Self-Control by Effector CD8⁺ T Cells In infected peripheral tissues, some effector CD8⁺ (CTL) T cells receive additional local signals including antigen, CD4⁺ T cell-derived IL-2, and innate cell-derived IL-27, and transiently acquire the ability to secrete IL-10 in a Blimp-1-dependent manner. CTL-derived IL-10 is critical to control local inflammation and tissue damage.