A soluble factor from Trypanosoma brucei rhodesiense that prevents progression of activated human T lymphocytes through the cell cycle.
African sleeping sickness is accompanied by a severe immunosuppression. As part of our efforts to examine the mechanisms by which this suppressive state is induced, we studied alterations in human T-lymphocyte function caused by Trypanosoma brucei rhodesiense. To this end, we used an in vitro system in which phytohaemagglutinin (PHA)-stimulated human peripheral blood mononuclear cells (PBMC) were cultured in a medium containing soluble, non-dialysable parasite products. We were able to demonstrate significant suppression of both lympho-proliferation and interleukin-2 receptor (IL-2R) expression. These effects were found to be dose-dependent and reversible after 48 hr of culture. The suppressive effects of living trypanosomes and the soluble parasite products on lympho-proliferation and interleukin-2 receptor expression were similar in that both precluded the entry of PHA-activated PBMC into the cell cycle. Eighty to ninety-eight per cent of the activated cells remained arrested in the G0/G1a (early G1) phase even 48 hr after stimulation, i.e. when last tested. Parasite-induced expression could not be overcome by the addition of recombinant human IL-2. These results suggest that immunosuppression associated with African trypanosomiasis may result from parasite-induced alteration of very early events during lymphocyte activation, leading to a virtually complete block in cell cycle progression and inhibition of IL-2R expression.
Sztein
M B
MB
Department of Pediatrics, University of Maryland School of Medicine, Baltimore 21201.
Kierszenbaum
F
F
D000818:Animals; D001685:Biological Factors / Q000276:immunology; D002453:Cell Cycle / Q000276:immunology; D002478:Cells, Cultured; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D010835:Phytohemagglutinins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014346:Trypanosoma brucei brucei / Q000276:immunology; D014353:Trypanosomiasis, African / Q000276:immunology*
D001685:Biological Factors; D010835:Phytohemagglutinins