The dynamics of effector T cells and Foxp3+ regulatory T cells in the promotion and regulation of autoimmune encephalomyelitis

Abstract

The Th1/Th2 paradigm of T helper cell subsets had to be revised when IL-17 producing T cells (Th17) were identified as a distinct T helper cell lineage. Th17 cells are very efficient inducers of tissue inflammation and crucial initiators of organ-specific autoimmunity. Whereas Th17 cells promote autoimmune tissue inflammation, Foxp3+ regulatory T cells (T-reg) are necessary and sufficient to prevent autoimmunity throughout the life span of an individual. Here, we review recent findings of how responses of effector T cells and T-reg cells with a defined antigen-specificity develop in autoimmune encephalomyelitis. Moreover, Th17 cells and Foxp3+ T-reg seem to be dichotomously related in that TGF-beta induces Foxp3 in naïve T cells, but TGF-beta and IL-6 together drive the generation of Th17 cells. Thus, we give an overview of how Th17 cells, induced Foxp3+ T-reg, as well as how naturally occurring T-reg cells might cooperate to promote and regulate autoimmune inflammation of the central nervous system (CNS). The monitoring of the population dynamics of these T cell subsets in reporter mice in vivo will enable us to revisit the pathogenic concept of autoimmune inflammation in the CNS and design rational and phase-specific therapeutic interventions.