The dynamics of effector T cells and Foxp3+ regulatory T cells in the promotion and regulation of autoimmune encephalomyelitis.
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.
Korn
Thomas
T
Brigham and Women's Hospital, Center for Neurologic Diseases, Harvard Medical School, Boston, MA 02115, USA. tkorn@rics.bwh.harvard.edu
Anderson
Ana C
AC
Bettelli
Estelle
E
Oukka
Mohamed
M
D000818:Animals; D015551:Autoimmunity; D002454:Cell Differentiation; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology* / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000032:analysis* / Q000502:physiology; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology; D020381:Interleukin-17 / Q000502:physiology*; D053759:Interleukin-23 / Q000502:physiology; D007378:Interleukins / Q000502:physiology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000502:physiology
D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; C486767:Il27 protein, mouse; D007375:Interleukin-1; D020381:Interleukin-17; D053759:Interleukin-23; D007378:Interleukins; D016212:Transforming Growth Factor beta