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2008
Parietti Véronique, Monneaux Fanny, Décossas Marion, Muller Sylviane
Function of CD4+,CD25+ Treg cells in MRL/lpr mice is compromised by intrinsic defects in antigen-presenting cells and effector Ŧ cells Journal Article
In: Arthritis and Rheumatism, vol. 58, no. 6, pp. 1751–1761, 2008, ISSN: 0004-3591.
Abstract | Links | BibTeX | Tags: Animal, Animals, Antigen-Presenting Cells, Antigens, B7-1 Antigen, B7-2 Antigen, CD, Cell Communication, Cells, Coculture Techniques, CTLA-4 Antigen, Cultured, Disease Models, Female, I2CT, Interleukin-1, Interleukin-2 Receptor alpha Subunit, Lupus Erythematosus, Mice, Monneaux, Regulatory, Systemic, T-Lymphocyte Subsets, T-Lymphocytes, Team-Dumortier
@article{parietti_function_2008,
title = {Function of CD4+,CD25+ Treg cells in MRL/lpr mice is compromised by intrinsic defects in antigen-presenting cells and effector Ŧ cells},
author = {Véronique Parietti and Fanny Monneaux and Marion Décossas and Sylviane Muller},
doi = {10.1002/art.23464},
issn = {0004-3591},
year = {2008},
date = {2008-06-01},
journal = {Arthritis and Rheumatism},
volume = {58},
number = {6},
pages = {1751--1761},
abstract = {OBJECTIVE: Naturally occurring CD4+,CD25+ Treg cells are central in the maintenance of peripheral tolerance. Impaired activity and/or a lower frequency of these cells is involved in the emergence of autoimmunity. We undertook this study to analyze relative proportions and functional alterations of Treg cells in MRL/lpr mice.
METHODS: The frequency of CD4+,CD25+ T cells in the peripheral blood of healthy and autoimmune mice was compared by flow cytometry. The capacity of CD4+,CD25+ T cells to inhibit the proliferation and cytokine secretion of CD4+,CD25- T cells was assessed after polyclonal activation.
RESULTS: MRL/lpr mice exhibited a normal percentage of CD4+,CD25 high T cells, and forkhead box P3 messenger RNA and protein expression in Treg cells was not altered. However, MRL/lpr Treg cells displayed a reduced capacity to suppress proliferation and to inhibit interferon-gamma secretion by syngeneic effector CD4+,CD25- T cells, as compared with syngeneic cocultures of CBA/J T cells. Moreover, effector MRL/lpr CD4+,CD25- T cells were substantially less susceptible to suppression even when cultured with CBA/J or MRL/lpr Treg cells. Crossover experiments led us to conclude that in MRL/lpr mice, each partner engaged in T cell regulation displays altered functions. Molecules involved in suppressive mechanisms (CTLA-4 and CD80/CD86) are underexpressed, and antigen-presenting cells (APCs) produce raised levels of interleukin-6, which is known to abrogate suppression.
CONCLUSION: Our results suggest that although the frequency and phenotype of Treg cells in MRL/lpr mice are similar to those in normal mice, Treg cells in MRL/lpr mice are not properly stimulated by APCs and are unable to suppress proinflammatory cytokine secretion from effector T cells.},
keywords = {Animal, Animals, Antigen-Presenting Cells, Antigens, B7-1 Antigen, B7-2 Antigen, CD, Cell Communication, Cells, Coculture Techniques, CTLA-4 Antigen, Cultured, Disease Models, Female, I2CT, Interleukin-1, Interleukin-2 Receptor alpha Subunit, Lupus Erythematosus, Mice, Monneaux, Regulatory, Systemic, T-Lymphocyte Subsets, T-Lymphocytes, Team-Dumortier},
pubstate = {published},
tppubtype = {article}
}
OBJECTIVE: Naturally occurring CD4+,CD25+ Treg cells are central in the maintenance of peripheral tolerance. Impaired activity and/or a lower frequency of these cells is involved in the emergence of autoimmunity. We undertook this study to analyze relative proportions and functional alterations of Treg cells in MRL/lpr mice.
METHODS: The frequency of CD4+,CD25+ T cells in the peripheral blood of healthy and autoimmune mice was compared by flow cytometry. The capacity of CD4+,CD25+ T cells to inhibit the proliferation and cytokine secretion of CD4+,CD25- T cells was assessed after polyclonal activation.
RESULTS: MRL/lpr mice exhibited a normal percentage of CD4+,CD25 high T cells, and forkhead box P3 messenger RNA and protein expression in Treg cells was not altered. However, MRL/lpr Treg cells displayed a reduced capacity to suppress proliferation and to inhibit interferon-gamma secretion by syngeneic effector CD4+,CD25- T cells, as compared with syngeneic cocultures of CBA/J T cells. Moreover, effector MRL/lpr CD4+,CD25- T cells were substantially less susceptible to suppression even when cultured with CBA/J or MRL/lpr Treg cells. Crossover experiments led us to conclude that in MRL/lpr mice, each partner engaged in T cell regulation displays altered functions. Molecules involved in suppressive mechanisms (CTLA-4 and CD80/CD86) are underexpressed, and antigen-presenting cells (APCs) produce raised levels of interleukin-6, which is known to abrogate suppression.
CONCLUSION: Our results suggest that although the frequency and phenotype of Treg cells in MRL/lpr mice are similar to those in normal mice, Treg cells in MRL/lpr mice are not properly stimulated by APCs and are unable to suppress proinflammatory cytokine secretion from effector T cells.
METHODS: The frequency of CD4+,CD25+ T cells in the peripheral blood of healthy and autoimmune mice was compared by flow cytometry. The capacity of CD4+,CD25+ T cells to inhibit the proliferation and cytokine secretion of CD4+,CD25- T cells was assessed after polyclonal activation.
RESULTS: MRL/lpr mice exhibited a normal percentage of CD4+,CD25 high T cells, and forkhead box P3 messenger RNA and protein expression in Treg cells was not altered. However, MRL/lpr Treg cells displayed a reduced capacity to suppress proliferation and to inhibit interferon-gamma secretion by syngeneic effector CD4+,CD25- T cells, as compared with syngeneic cocultures of CBA/J T cells. Moreover, effector MRL/lpr CD4+,CD25- T cells were substantially less susceptible to suppression even when cultured with CBA/J or MRL/lpr Treg cells. Crossover experiments led us to conclude that in MRL/lpr mice, each partner engaged in T cell regulation displays altered functions. Molecules involved in suppressive mechanisms (CTLA-4 and CD80/CD86) are underexpressed, and antigen-presenting cells (APCs) produce raised levels of interleukin-6, which is known to abrogate suppression.
CONCLUSION: Our results suggest that although the frequency and phenotype of Treg cells in MRL/lpr mice are similar to those in normal mice, Treg cells in MRL/lpr mice are not properly stimulated by APCs and are unable to suppress proinflammatory cytokine secretion from effector T cells.
2007
Habib Mohammed, Rivas Magali Noval, Chamekh Mustapha, Wieckowski Sébastien, Sun Weimin, Bianco Alberto, Trouche Nathalie, Chaloin Olivier, Dumortier Hélène, Goldman Michel, Guichard Gilles, Fournel Sylvie, Vray Bernard
In: Journal of Immunology (Baltimore, Md.: 1950), vol. 178, no. 11, pp. 6700–6704, 2007, ISSN: 0022-1767.
Abstract | Links | BibTeX | Tags: Animals, CD40 Antigens, CD40 Ligand, Cell Line, Cells, Chagas Disease, Cultured, Dumortier, I2CT, Inbred BALB C, Inbred C57BL, Interferon-gamma, Knockout, Mice, Molecular Mimicry, Parasitemia, T-Lymphocyte Subsets, Team-Bianco, Team-Dumortier, Trypanosoma cruzi
@article{habib_cutting_2007,
title = {Cutting edge: small molecule CD40 ligand mimetics promote control of parasitemia and enhance Ŧ cells producing IFN-gamma during experimental Trypanosoma cruzi infection},
author = {Mohammed Habib and Magali Noval Rivas and Mustapha Chamekh and Sébastien Wieckowski and Weimin Sun and Alberto Bianco and Nathalie Trouche and Olivier Chaloin and Hélène Dumortier and Michel Goldman and Gilles Guichard and Sylvie Fournel and Bernard Vray},
doi = {10.4049/jimmunol.178.11.6700},
issn = {0022-1767},
year = {2007},
date = {2007-06-01},
journal = {Journal of Immunology (Baltimore, Md.: 1950)},
volume = {178},
number = {11},
pages = {6700--6704},
abstract = {Host resistance to Trypanosoma cruzi infection depends on a type 1 response characterized by a strong production of IL-12 and IFN-gamma. Amplifying this response through CD40 triggering results in control of parasitemia. Two newly synthesized molecules (textless3 kDa) mimicking trimeric CD40L (mini CD40Ls(-1) and (-2)) bind to CD40, activate murine dendritic cells, and elicit IL-12 production. Wild-type but not CD40 knockout mice exhibited a sharp decrease of parasitemia and mortality when inoculated with T. cruzi mixed with miniCD40Ls. Moreover, the immunosuppression induced by T. cruzi infection was impaired in mice treated with miniCD40Ls, as shown by proliferation of splenic lymphocytes, percentage of CD8(+) T cells, and IFN-gamma production. Mice surviving T. cruzi infection in the presence of miniCD40L(-1) were immunized against a challenge infection. Our results indicate that CD40L mimetics are effective in vivo and promote the control of T. cruzi infection by overcoming the immunosuppression usually induced by the parasites.},
keywords = {Animals, CD40 Antigens, CD40 Ligand, Cell Line, Cells, Chagas Disease, Cultured, Dumortier, I2CT, Inbred BALB C, Inbred C57BL, Interferon-gamma, Knockout, Mice, Molecular Mimicry, Parasitemia, T-Lymphocyte Subsets, Team-Bianco, Team-Dumortier, Trypanosoma cruzi},
pubstate = {published},
tppubtype = {article}
}
Host resistance to Trypanosoma cruzi infection depends on a type 1 response characterized by a strong production of IL-12 and IFN-gamma. Amplifying this response through CD40 triggering results in control of parasitemia. Two newly synthesized molecules (textless3 kDa) mimicking trimeric CD40L (mini CD40Ls(-1) and (-2)) bind to CD40, activate murine dendritic cells, and elicit IL-12 production. Wild-type but not CD40 knockout mice exhibited a sharp decrease of parasitemia and mortality when inoculated with T. cruzi mixed with miniCD40Ls. Moreover, the immunosuppression induced by T. cruzi infection was impaired in mice treated with miniCD40Ls, as shown by proliferation of splenic lymphocytes, percentage of CD8(+) T cells, and IFN-gamma production. Mice surviving T. cruzi infection in the presence of miniCD40L(-1) were immunized against a challenge infection. Our results indicate that CD40L mimetics are effective in vivo and promote the control of T. cruzi infection by overcoming the immunosuppression usually induced by the parasites.
Parietti Véronique, Chifflot Hélène, Muller Sylviane, Monneaux Fanny
Regulatory Ŧ cells and systemic lupus erythematosus Journal Article
In: Annals of the New York Academy of Sciences, vol. 1108, pp. 64–75, 2007, ISSN: 0077-8923.
Abstract | Links | BibTeX | Tags: Animals, Autoimmunity, Humans, I2CT, Immune Tolerance, Lupus Erythematosus, Monneaux, Regulatory, Systemic, T-Lymphocyte Subsets, T-Lymphocytes, Team-Dumortier
@article{parietti_regulatory_2007,
title = {Regulatory Ŧ cells and systemic lupus erythematosus},
author = {Véronique Parietti and Hélène Chifflot and Sylviane Muller and Fanny Monneaux},
doi = {10.1196/annals.1422.007},
issn = {0077-8923},
year = {2007},
date = {2007-01-01},
journal = {Annals of the New York Academy of Sciences},
volume = {1108},
pages = {64--75},
abstract = {Regulatory T cells, especially CD4+CD25+ T cells, "natural killer" T cells and gammadelta T cells, are central in the maintenance of peripheral tolerance and the protection from the development of autoimmune diseases. Numerical or functional modifications of these cell populations were demonstrated to lead to the breakdown of tolerance and the emergence of autoimmunity. Involvement of regulatory T cells in the pathogenesis of systemic autoimmune diseases, such as systemic lupus erythematosus, might be of first importance. In murine models and patients with lupus, these regulatory T cells seem to be reduced in number. Functional deficiencies have also been described in a few studies. A better knowledge of regulatory T cell functional properties in systemic autoimmune diseases is essential to manipulate these cells and hopefully to restore immune tolerance.},
keywords = {Animals, Autoimmunity, Humans, I2CT, Immune Tolerance, Lupus Erythematosus, Monneaux, Regulatory, Systemic, T-Lymphocyte Subsets, T-Lymphocytes, Team-Dumortier},
pubstate = {published},
tppubtype = {article}
}
Regulatory T cells, especially CD4+CD25+ T cells, "natural killer" T cells and gammadelta T cells, are central in the maintenance of peripheral tolerance and the protection from the development of autoimmune diseases. Numerical or functional modifications of these cell populations were demonstrated to lead to the breakdown of tolerance and the emergence of autoimmunity. Involvement of regulatory T cells in the pathogenesis of systemic autoimmune diseases, such as systemic lupus erythematosus, might be of first importance. In murine models and patients with lupus, these regulatory T cells seem to be reduced in number. Functional deficiencies have also been described in a few studies. A better knowledge of regulatory T cell functional properties in systemic autoimmune diseases is essential to manipulate these cells and hopefully to restore immune tolerance.
