In vitro simulation of immuno-suppression caused by Trypanosoma brucei: Active involvement of gamma interferon and tumor necrosis factor in the pathway of suppression
Experimental infections of mice with the African trypanosome Trypanosoma brucei lead to a profound state of T-cell unresponsiveness in the lymph node cell (LNC) compartment. This suppression is mediated by macrophage-like cells which inhibit interleukin 2 (IL-2) secretion and down-regulate IL-2 rece...
| Main Authors: | , , , , , |
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| Format: | Journal Article |
| Language: | Inglés |
| Published: |
1996
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| Online Access: | https://hdl.handle.net/10568/28753 |
| _version_ | 1855519683187310592 |
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| author | Darji, A. Beschin, A. Sileghem, M.R. Heremans, H. Brys, L. Baetselier, P. de |
| author_browse | Baetselier, P. de Beschin, A. Brys, L. Darji, A. Heremans, H. Sileghem, M.R. |
| author_facet | Darji, A. Beschin, A. Sileghem, M.R. Heremans, H. Brys, L. Baetselier, P. de |
| author_sort | Darji, A. |
| collection | Repository of Agricultural Research Outputs (CGSpace) |
| description | Experimental infections of mice with the African trypanosome Trypanosoma brucei lead to a profound state of T-cell unresponsiveness in the lymph node cell (LNC) compartment. This suppression is mediated by macrophage-like cells which inhibit interleukin 2 (IL-2) secretion and down-regulate IL-2 receptor expression (M. Sileghem, A. Darji, R. Hamers, M. Van de Winkel, and De Baetselier, Eur. J. Immunol. 19:829- 835, 1989). Similar suppressive cells can be generated in vitro by pulsing 2C11-12 macrophage hybridoma cells with opsonized T. brucei parasites (2C11-12P cells). Cocultures of 2C11-12P cells and LNCs secrete higher levels of gamma interferon (IFN-gamma), and the hyperproduction of IFN-gamma was found to be confined to CD8+ lymphoid cells. Elimination of CD8+ cells from cocultures of 2C11-12P cells and LNCs restores the T-cell proliferative response. Furthermore, addition of neutralizing anti-IFN-gamma antibodies to the cocultures reduces the level of suppression and concomitantly restores the level of IL-2 receptor expression. Hence, IFN-gamma plays a cardinal role in this in vitro model for T. brucei-elicited immunosuppression. Cocultures of LNCs and 2C11-12P cells in a two-chamber culture system further demonstrated that cell-cell contact is required for hyperproduction of IFN-gamma and, moreover, that IFN-gamma cooperates with a 2C11-12P- derived diffusible factor to exert its suppressive activity. Finally, tumor necrosis factor alpha (TNF-alpha produced by 2C11-12P cells was found to be implicated in the hyperproduction of IFN-gamma, since addition of neutralizing anti-TNF-alpha antibodies to cocultures reduced the level of suppression and concomitantly abrogated the hyperproduction of IFN-gamma. Collectively, our findings indicate that T. brucei-elicited suppressive 2C11-12 macrophage cells differentially influence T-cell subpopulations: (i) CD8+ cells are signaled via cell- cell contact to produce IFN-gamma, and TNF-alpha is implicated in this process, and (ii) locally produced IFN-gamma and macrophage-released factors act in concert to inhibit CD4+ and CD8+ T-cell proliferative responses. |
| format | Journal Article |
| id | CGSpace28753 |
| institution | CGIAR Consortium |
| language | Inglés |
| publishDate | 1996 |
| publishDateRange | 1996 |
| publishDateSort | 1996 |
| record_format | dspace |
| spelling | CGSpace287532022-01-29T16:16:45Z In vitro simulation of immuno-suppression caused by Trypanosoma brucei: Active involvement of gamma interferon and tumor necrosis factor in the pathway of suppression Darji, A. Beschin, A. Sileghem, M.R. Heremans, H. Brys, L. Baetselier, P. de trypanosoma brucei experimental infection in vitro simulation immunosuppression cytokines Experimental infections of mice with the African trypanosome Trypanosoma brucei lead to a profound state of T-cell unresponsiveness in the lymph node cell (LNC) compartment. This suppression is mediated by macrophage-like cells which inhibit interleukin 2 (IL-2) secretion and down-regulate IL-2 receptor expression (M. Sileghem, A. Darji, R. Hamers, M. Van de Winkel, and De Baetselier, Eur. J. Immunol. 19:829- 835, 1989). Similar suppressive cells can be generated in vitro by pulsing 2C11-12 macrophage hybridoma cells with opsonized T. brucei parasites (2C11-12P cells). Cocultures of 2C11-12P cells and LNCs secrete higher levels of gamma interferon (IFN-gamma), and the hyperproduction of IFN-gamma was found to be confined to CD8+ lymphoid cells. Elimination of CD8+ cells from cocultures of 2C11-12P cells and LNCs restores the T-cell proliferative response. Furthermore, addition of neutralizing anti-IFN-gamma antibodies to the cocultures reduces the level of suppression and concomitantly restores the level of IL-2 receptor expression. Hence, IFN-gamma plays a cardinal role in this in vitro model for T. brucei-elicited immunosuppression. Cocultures of LNCs and 2C11-12P cells in a two-chamber culture system further demonstrated that cell-cell contact is required for hyperproduction of IFN-gamma and, moreover, that IFN-gamma cooperates with a 2C11-12P- derived diffusible factor to exert its suppressive activity. Finally, tumor necrosis factor alpha (TNF-alpha produced by 2C11-12P cells was found to be implicated in the hyperproduction of IFN-gamma, since addition of neutralizing anti-TNF-alpha antibodies to cocultures reduced the level of suppression and concomitantly abrogated the hyperproduction of IFN-gamma. Collectively, our findings indicate that T. brucei-elicited suppressive 2C11-12 macrophage cells differentially influence T-cell subpopulations: (i) CD8+ cells are signaled via cell- cell contact to produce IFN-gamma, and TNF-alpha is implicated in this process, and (ii) locally produced IFN-gamma and macrophage-released factors act in concert to inhibit CD4+ and CD8+ T-cell proliferative responses. 1996 2013-05-06T07:01:20Z 2013-05-06T07:01:20Z Journal Article https://hdl.handle.net/10568/28753 en Limited Access Infection and Immunity;64(6): 1937-1943 |
| spellingShingle | trypanosoma brucei experimental infection in vitro simulation immunosuppression cytokines Darji, A. Beschin, A. Sileghem, M.R. Heremans, H. Brys, L. Baetselier, P. de In vitro simulation of immuno-suppression caused by Trypanosoma brucei: Active involvement of gamma interferon and tumor necrosis factor in the pathway of suppression |
| title | In vitro simulation of immuno-suppression caused by Trypanosoma brucei: Active involvement of gamma interferon and tumor necrosis factor in the pathway of suppression |
| title_full | In vitro simulation of immuno-suppression caused by Trypanosoma brucei: Active involvement of gamma interferon and tumor necrosis factor in the pathway of suppression |
| title_fullStr | In vitro simulation of immuno-suppression caused by Trypanosoma brucei: Active involvement of gamma interferon and tumor necrosis factor in the pathway of suppression |
| title_full_unstemmed | In vitro simulation of immuno-suppression caused by Trypanosoma brucei: Active involvement of gamma interferon and tumor necrosis factor in the pathway of suppression |
| title_short | In vitro simulation of immuno-suppression caused by Trypanosoma brucei: Active involvement of gamma interferon and tumor necrosis factor in the pathway of suppression |
| title_sort | in vitro simulation of immuno suppression caused by trypanosoma brucei active involvement of gamma interferon and tumor necrosis factor in the pathway of suppression |
| topic | trypanosoma brucei experimental infection in vitro simulation immunosuppression cytokines |
| url | https://hdl.handle.net/10568/28753 |
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