TY - JOUR
T1 - Making regulatory T cells with defined antigen specificity
T2 - Role in autoimmunity and cancer
AU - Kretschmer, Karsten
AU - Apostolou, Irina
AU - Jaeckel, Elmar
AU - Khazaie, Khashayarsha
AU - Von Boehmer, Harald
PY - 2006/8
Y1 - 2006/8
N2 - There is increasing evidence that agonist ligand presentation either intrathymically or extrathymically plays a crucial if not essential role in the generation of regulatory T cells (Tregs). Thus, it is possible to induce Tregs of any desired specificity in vivo. The same goal can be achieved in vitro by expanding antigen-specific CD4+ T cells and retrovirally transducing them. In contrast, in vitro expansion of Tregs is Limited to antigens that have resulted in Treg generation in vivo. Antigen-specific Tregs can be used in cellular therapy with the goal to prevent autoimmune disease or even to interfere with established autoimmunity. The latter requires that the Tregs can suppress effector cells that have already caused harm, which is possible because of the antigen-dependent homing properties of Tregs, i.e. these cells can accumulate in antigen-draining lymph nodes and exit into inflamed tissue. Generally, the in vivo interference is dependent on cytokines such as transforming growth factor-β and interleukin-10 that were dispensable in in vivo analysis of immunosuppression. The precise mechanisms of suppression remain enigmatic, however, but may be further elucidated by the molecular analysis of suppressed versus non-suppressed T cells.
AB - There is increasing evidence that agonist ligand presentation either intrathymically or extrathymically plays a crucial if not essential role in the generation of regulatory T cells (Tregs). Thus, it is possible to induce Tregs of any desired specificity in vivo. The same goal can be achieved in vitro by expanding antigen-specific CD4+ T cells and retrovirally transducing them. In contrast, in vitro expansion of Tregs is Limited to antigens that have resulted in Treg generation in vivo. Antigen-specific Tregs can be used in cellular therapy with the goal to prevent autoimmune disease or even to interfere with established autoimmunity. The latter requires that the Tregs can suppress effector cells that have already caused harm, which is possible because of the antigen-dependent homing properties of Tregs, i.e. these cells can accumulate in antigen-draining lymph nodes and exit into inflamed tissue. Generally, the in vivo interference is dependent on cytokines such as transforming growth factor-β and interleukin-10 that were dispensable in in vivo analysis of immunosuppression. The precise mechanisms of suppression remain enigmatic, however, but may be further elucidated by the molecular analysis of suppressed versus non-suppressed T cells.
KW - Autoimmune suppression
KW - Foxp3
KW - Regulatory T cells
KW - Transforming growth factor-β
UR - http://www.scopus.com/inward/record.url?scp=33746351318&partnerID=8YFLogxK
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U2 - 10.1111/j.0105-2896.2006.00411.x
DO - 10.1111/j.0105-2896.2006.00411.x
M3 - Review article
C2 - 16903913
AN - SCOPUS:33746351318
SN - 0105-2896
VL - 212
SP - 163
EP - 169
JO - Immunological Reviews
JF - Immunological Reviews
ER -