An integrated view of suppressor T cell subsets in immunoregulation
Hong Jiang, Leonard Chess
Hong Jiang, Leonard Chess
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Review Series Introduction

An integrated view of suppressor T cell subsets in immunoregulation

Abstract

The immune system evolved to protect organisms from a virtually infinite variety of disease-causing agents but to avoid harmful responses to self. Because immune protective mechanisms include the elaboration of potent inflammatory molecules, antibodies, and killer cell activation — which together can not only destroy invading microorganisms, pathogenic autoreactive cells, and tumors, but also mortally injure normal cells — the immune system is inherently a “double-edged sword” and must be tightly regulated. Immune response regulation includes homeostatic mechanisms intrinsic to the activation and differentiation of antigen-triggered immunocompetent cells and extrinsic mechanisms mediated by suppressor cells. This review series will focus on recent advances indicating that distinct subsets of regulatory CD4+ and CD8+ T cells as well as NK T cells control the outgrowth of potentially pathogenic antigen-reactive T cells and will highlight the evidence that these suppressor T cells may play potentially important clinical roles in preventing and treating immune-mediated disease. Here we provide a historical overview of suppressor cells and the experimental basis for the existence of functionally and phenotypically distinct suppressor subsets. Finally, we will speculate on how the distinct suppressor cell subsets may function in concert to regulate immune responses.

Authors

Hong Jiang, Leonard Chess

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Model of cognate interactions in the induction and function of Qa-1–rest...
Model of cognate interactions in the induction and function of Qa-1–restricted regulatory CD8+ T cells. (A) Initial activation of CD4+ T cell TCRs with peptide–MHC complexes induces the expression of Qa-1 bound with a variety of self-peptides on the surface of the CD4+ T cells. (B) Anti–Qa-1–self-peptide CD8+ precursor T cells are activated by Qa-1–expressing CD4+ T cells. The Qa-1–restricted CD8+ Tregs selectively downregulate certain but not all antigen-activated CD4+ T cells based on the specific recognition of Qa-1–self-peptide complexes expressed on certain CD4+ T cells by TCR αβ on the CD8+ T cells. In this regard, we have demonstrated in the EAE model that self-reactive CD4+ T cells, which are selectively downregulated by the CD8+ T cells, are enriched in potentially pathogenic self-reactive T cell clones (9).