TY - JOUR
T1 - The dynamics of effector T cells and Foxp3+ regulatory T cells in the promotion and regulation of autoimmune encephalomyelitis
AU - Korn, Thomas
AU - Anderson, Ana C.
AU - Bettelli, Estelle
AU - Oukka, Mohamed
N1 - Funding Information:
This work was supported by grants from the National Multiple Sclerosis Society, the National Institutes of Health, the Juvenile Diabetes Research Foundation Center for Immunological Tolerance at Harvard, and the Deutsche Forschungsgemeinschaft.
PY - 2007/11
Y1 - 2007/11
N2 - 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-β induces Foxp3 in naïve T cells, but TGF-β 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.
AB - 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-β induces Foxp3 in naïve T cells, but TGF-β 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.
KW - Experimental autoimmune encephalomyelitis
KW - Foxp3
KW - Regulatory T cell
KW - Th17 cell
UR - http://www.scopus.com/inward/record.url?scp=35848929058&partnerID=8YFLogxK
U2 - 10.1016/j.jneuroim.2007.09.009
DO - 10.1016/j.jneuroim.2007.09.009
M3 - Review article
C2 - 17916388
AN - SCOPUS:35848929058
SN - 0165-5728
VL - 191
SP - 51
EP - 60
JO - Journal of Neuroimmunology
JF - Journal of Neuroimmunology
IS - 1-2
ER -