Mechanisms underlying trypanosome-elicited immunosuppression.

TitleMechanisms underlying trypanosome-elicited immunosuppression.
Publication TypeJournal Article
Year of Publication1992
AuthorsDarji, A., R. Lucas, S. Magez, E. Torreele, J. Palacios, M. Sileghem, B. E Songa, R. Hamers, and P. De Baetselier
JournalAnn Soc Belg Med Trop
Volume72 Suppl 1
Pagination27-38
Date Published1992
ISSN0772-4128
KeywordsAnimals, Immune Tolerance, Interferon-gamma, Interleukin-2, Lymphocyte Activation, Macrophages, Mice, Receptors, Interleukin-2, T-Lymphocytes, Trypanosoma brucei brucei
Abstract

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.

Alternate JournalAnn Soc Belg Med Trop
PubMed ID1417167