• Citer

In vitro simulation of immunosuppression caused by Trypanosoma brucei: Active involvement of gamma interferon and tumor necrosis factor in the pathway of suppression

par Darji, Ayub;Beschin, Alain ;Sileghem, Maarten;Heremans, Hubertine;Brys, Lea;De Baetselier, Patrick
Référence Infection and immunity, 64, 6, page (1937-1943)
Publication Publié, 1996-06

Article révisé par les pairs

• Détails
• Contenu

Résumé :

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 P. 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-γ), and the hyperproduction of IFN-γ 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-γ antibodies to the cocultures reduces the level of suppression and concomitantly restores the level of IL-2 receptor expression. Hence, IFN-γ 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-γ and, moreover, that IFN-γ cooperates with a 2C11-12P-derived diffusible factor to exert its suppressive activity. Finally, tumor necrosis factor alpha (TNF-α) produced by 2C11-12P cells was found to be implicated in the hyperproduction of IFN-γ, since addition of neutralizing anti-TNF-α antibodies to cocultures reduced the level of suppression and concomitantly abrogated the hyperproduction of IFN-γ. 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-γ, and TNF-α is implicated in this process, and (ii) locally produced IFN-γ and macrophage- released factors act in concert to inhibit CD4+ and CD8+ T-cell proliferative responses.