Mechanisms underlying trypanosome-elicited immunosuppression.

A. Darji, Rudolf Lucas, S. Magez, E. Torreele, J. Palacios, M. Sileghem, E. Bajyana Songa, R. Hamers, P. De Baetselier

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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.

Original languageEnglish (US)
Pages (from-to)27-38
Number of pages12
JournalAnnales de la Société belge de médecine tropicale
Volume72 Suppl 1
Publication statusPublished - Jan 1 1992
Externally publishedYes

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ASJC Scopus subject areas

  • Infectious Diseases

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Darji, A., Lucas, R., Magez, S., Torreele, E., Palacios, J., Sileghem, M., ... De Baetselier, P. (1992). Mechanisms underlying trypanosome-elicited immunosuppression. Annales de la Société belge de médecine tropicale, 72 Suppl 1, 27-38.