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Crosstalk between autoreactive T cells and alveolar type II epithelial cells in inflammation and tolerance

von Dr. Marcus Gereke

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[1.] Mag/Fragment 030 01 - Diskussion
Zuletzt bearbeitet: 2014-03-10 13:36:04 Hindemith
Bluestone Abbas 2003, Fragment, Gesichtet, Mag, SMWFragment, Schutzlevel sysop, Verschleierung

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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).

Anmerkungen

No mention of the source. Directly followed by Fragment_030_13.

Sichter
Schumann

[2.] Mag/Fragment 030 13 - Diskussion
Zuletzt bearbeitet: 2014-03-10 13:25:32 Hindemith
Fragment, Gesichtet, Mag, SMWFragment, Schutzlevel sysop, Shevach 2002, Verschleierung

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Several different in vitro protocols have been described over the past few years that result in the generation of suppressor T cells. The activation of mouse or human CD4+ T cells in vitro in the presence of IL-10 has been shown to result in the generation of T cell clones with a cytokine profile different from that of T helper 1 (TH1) or T helper 2 (TH2) cells. Functionally, these T cell clones have inhibitory effects on antigen specific activation of naïve T cells that are mediated partially by IL-10 and TGF-β, and were termed T regulatory 1 (TR1) cells (Groux et al., 1997). A related approach for the generation of suppressor T cells in vitro involves the stimulation of naïve T cells with immature (im)DC. Surprisingly, although these cells produce IL-10, their suppressor phenotype resembles that of CD25+ T cells, as it is contact dependent, antigen non-specific and APC-independent. Immature DC are the ideal population to prime regulatory T cells as they are deficient in costimulatory molecules, and priming with antigen-imDC complexes might even be able to downregulate pre-existing antigen specific immune responses (Dhodapkar et al., 2001). Exposure to TGF-β has also been reported to facilitate the differentiation/expansion of suppressor T cell populations in vitro (Yamagiwa et al.; 2001).

Dhodapkar MV, Steinman RM, Krasovsky J, Munz C, Bhardwaj N. Antigen-specific inhibition of effector T cell function in humans after injection of immature dendritic cells. J Exp Med. 2001 Jan 15; 193 (2): 233-8.

Groux H, O'Garra A, Bigler M, Rouleau M, Antonenko S, de Vries JE, Roncarolo MG. A CD4+ T-cell subset inhibits antigen-specific T-cell responses and prevents colitis. Nature. 1997 Oct 16; 389 (6652): 737-42.

Yamagiwa S, Gray JD, Hashimoto S, Horwitz DA. A role for TGF-beta in the generation and expansion of CD4+CD25+ regulatory T cells from human peripheral blood. J Immunol. 2001 Jun 15; 166 (12): 7282-9.

Several different in vitro protocols have been described over the past few years that result in the generation of suppressor T cells (FIG. 1). The activation of human or mouse CD4+ T cells in vitro in the presence of IL-10 has been shown to result in the generation of T-cell clones with a cytokine profile that is different from that of T helper 1 (TH1) or TH2 cells.[...] Functionally, these T-cell clones have inhibitory effects on the antigen-specific activation of naive autologous T cells that are mediated partially by IL-10 and TGF-β. These new T cells were termed T regulatory 1 (TR1) cells67. [...]

A related approach for the generation of suppressor T cells in vitro involves the stimulation of naive T cells with iDCs. [...] Surprisingly, although these cells produced IL-10, their suppressor phenotype resembled that of CD25+ T cells, as it was contact-dependent, antigen non-specific and APC-independent. [...] Immature DCs are the ideal population to prime regulatory T cells as they are deficient in co-stimulatory molecules, and priming with antigen–iDC complexes might even be able to downregulate pre-existing antigen-specific immune responses70.

Exposure to TGF-β has also been reported to facilitate the differentiation/expansion of suppressor T-cell populations in vitro. [...]71


67. Groux, H. et al. A CD4+ T-cell subset inhibits antigen-specific TD-cell responses and prevents colitis. Nature 389, 737–742 (1997). The first definition of the TR1 population of regulatory T cells.

70. Dhodapkar, M. V., Steinman, R. M., Krasovsky, J., Munz, C. & Bhardwaj, N. Antigen-specific inhibition of effector T-cell function in humans after injection of immature dendritic cells. J. Exp. Med. 193, 233–238 (2001).

71. Yamagiwa, S., Gray, J. D., Hashimoto, S. & Horwitz, D. A. A role of TGF-β in the generation and expansion of CD4+CD25+ regulatory T cells from human peripheral blood. J. Immunol. 166, 7282–7289 (2001).

Anmerkungen

The source is not mentioned here although the text is identical up to marginal adaptations. Also the references to the literature are the same.

Sichter
(Hindemith), PlagProf:-)

[3.] Mag/Fragment 030 29 - Diskussion
Zuletzt bearbeitet: 2014-03-10 18:11:03 Graf Isolan
Bluestone Abbas 2003, Fragment, Gesichtet, Mag, SMWFragment, Schutzlevel sysop, Verschleierung

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Another possibility to induce regulatory T cells is antigen exposure by certain routes, including intranasal or oral administration. This strategy seems to induce selectively the appearance of T cells with this regulatory phenotype (Chen et al., 1994). For example, antigen exposure by certain routes, including intranasal or oral administration, seems to induce selectively the appearance of T cells with this regulatory phenotype21.

21. Chen, Y., Kuchroo, V. K., Inobe, J.-I., Hafler, D. A. & Weiner, H. L. Regulatory T-cell clones induced by oral tolerance: suppression of autoimmune encephalomyelitis. Science 265, 1237–1240 (1994).

Anmerkungen

A short fragment, following directly after Fragment 030 13. Could alternatively be rated as "Keine Wertung".

Sichter
(PlagProf:-)) Schumann


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