Mechanisms underlying trypanosome-elicited immunosuppression.
T-cell proliferative responses of lymph node cells are profoundly suppressed during experimental infections of mice with Trypanosoma brucei. The active suppression of lymph node T-cell proliferative responses is attributed to the coexistence of at least two unlinked suppressive mechanisms that block different T-cell regulatory steps and operate through different effector mechanisms. The generation of prostaglandin-producing macrophages is entirely responsible for the suppression of IL-2 production whereas the induction of a prostaglandin-independent suppressive mechanism accounts for the suppression of the expression of IL-2 receptors (IL-2R). Both mechanisms are mediated by the cells that co-purify which macrophages. Despite an impairment at the level of T-cell proliferation, lymph node cells from T. brucei infected animals produce substantial amounts of interferon-gamma (IFN-gamma) and this lymphokine participates in the down-regulation of IL-2R expression. T-brucei-pulsed macrophage cell lines acquire concomitantly the potential to suppress T-cell proliferative responses and to stimulate CD8+ T-cells to secrete IFN-gamma. The sensibilization of CD8+ T cells by T. brucei-pulsed macrophages might be mediated by TNF-alpha. Collectively, these results indicate that the uptake of T. brucei by macrophages, either in vivo or in vitro, results in the generation of suppressive cells that annihilate T-cell proliferative responses. Furthermore, at least two cytokines (i.e., TNF-alpha and IFN-gamma) are released during these interactions. Besides playing a role in the pathway of T-cell immunosuppression, TNF-alpha and IFN-gamma could also contribute to immunopathological features that occur during trypanosome infections.
Darji
A
A
Dept. of Cellular Immunology, Vrije Universiteit Brussel, Belgium.
Lucas
R
R
Magez
S
S
Torreele
E
E
Palacios
J
J
Sileghem
M
M
Bajyana Songa
E
E
Hamers
R
R
De Baetselier
P
P
D000818:Animals; D007108:Immune Tolerance; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*; D014346:Trypanosoma brucei brucei / Q000276:immunology*
D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D007371:Interferon-gamma