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Quelle: Bluestone_Abbas_2003 Seite(n): 254, Zeilen: col. 3: 13-35 |
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| 4.2 Adaptive regulatory T cells
These cells are generated from mature T cell populations under certain conditions of antigenic stimulation, and they can be induced ex vivo by culturing mature CD4+ T cells with antigen or polyclonal activators in the presence of immunosuppressive cytokines, namely IL-10 (Barrat et al., 2002; Levings et al., 2001). Similar to natural Treg cells, adaptive Treg cells originate from thymus, but they might be derived from classical T cell subsets or natural Treg cells. The level of expression of CD25 by adaptive Treg cell is variable, depending on the disease setting and the site of regulatory activity. Of note, adaptive Treg cells function in vivo in a cytokine dependent manner (Barrat et al., 2002; Chatenoud et al., 1997; Maloy and Powrie, 2001), so that these regulatory T cells are distinguished from natural Treg cells not by their origin (the thymus), but by their requirement for further differentiation as a consequence of exposure to antigen in a distinct immunological context. Barrat FJ, Cua DJ, Boonstra A, Richards DF, Crain C, Savelkoul HF, de Waal-Malefyt R, Coffman RL, Hawrylowicz CM, O'Garra A. In vitro generation of interleukin 10-producing regulatory CD4(+) T cells is induced by immunosuppressive drugs and inhibited by T helper type 1 (Th1)- and Th2-inducing cytokines. J Exp Med. 2002 Mar 4; 195 (5): 603-16. Chatenoud L, Primo J, Bach JF. CD3 antibody-induced dominant self tolerance in overtly diabetic NOD mice. J Immunol. 1997 Mar 15 ; 158 (6): 2947-54. Levings MK, Sangregorio R, Galbiati F, Squadrone S, de Waal Malefyt R, Roncarolo MG. IFN-alpha and IL-10 induce the differentiation of human type 1 T regulatory cells. J Immunol. 2001 May 1; 166 (9): 5530-9. Maloy KJ, Powrie F. Regulatory T cells in the control of immune pathology. Nat Immunol. 2001 Sep; 2 (9): 816-22. Review. |
Adaptive regulatory T cells. Additional populations of regulatory cells have been described in many settings of immunity18–21.These cells are generated from mature T-cell populations under certain conditions of antigenic stimulation, and they can be induced ex vivo by culturing mature CD4T+ T cells with antigen or polyclonal activators in the presence of immunosuppressive cytokines, notably IL-10 (REFS 5,22). Similar to natural TReg cells, adaptive TReg cells originate from the thymus, but they might be derived from classical T-cell subsets or natural TReg cells. The level of expression of CD25 by adaptive TReg cells is variable, depending on the disease setting and the site of regulatory activity23. Of note, adaptive TReg cells function in vivo in a cytokine-dependent manner5,6,18. So, we propose that adaptive TReg cells are distinguished from natural TReg cells not by their origin (the thymus), but rather by their requirement for further differentiation as a consequence of exposure to antigen in a distinct immunological context.
5. Barrat, F. J. et al. In vitro generation of interleukin-10-producing regulatory CD4+ T cells is induced by immunosuppressive drugs and inhibited by T helper type 1 (TH1)- and TH2-inducing cytokines. J. Exp. Med. 195, 603–616 (2002). 22. Levings, M. K., Sangregorio, R. & Roncarolo, M.-G. Human CD25+CD4+ T cells suppress naive and memory T-cell proliferation and can be expanded in vitro without loss of suppressor function. J. Exp. Med. 193, 1295–1302 (2001). 6. Chatenoud, L., Primo, J. & Bach, J. F. CD3 antibodyinduced dominant self-tolerance in overtly diabetic NOD mice. J. Immunol. 158, 2947–2954 (1997). 18. Maloy, K. J. & Powrie, F. Regulatory T cells in the control of immune pathology. Nature Immunol. 2, 816–822 (2001). |
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