Membrane fractions of trypanosomes mimic the immunosuppressive and mitogenic effects of living parasites on the host

Abstract

African trypanosomiasis in mice leads to profound changes in lymphoid tissues. In an attempt to define the nature of the trypanosome stimulus, we have studied the effect of radio-attenuated trypanosomes and their subcellular fractions in vivo. We find that relatively low doses of irradiated Trypanosoma brucei S42 injected into (CBA/H x C57B1/6)F1 mice mimicked the previously reported effects of infective parasites. 2 x 10(7) irradiated trypanosomes caused a greater than two-fold increase in spleen weight accompanied by a roughly 10-fold increase in background plaque forming cells (PFC) to sheep red blood cells (SRBC). The primary response to SRBC was significantly enhanced when priming was carried out on the day of trypanosome injection, but significantly suppressed when carried out 3 days later. Disruption of trypanosomes by freeze-thawing did not destroy their mitogenic or immunosuppressive activities. A membrane fraction collected by high speed centrifugation (150 000 x g) after removal of larger organelles at 12 000 x g retained both mitogenic and suppressive activities. The high speed supernatant lost the ability to enhance background PFC, but still caused partial immunosuppression with a much lower potency than the membrane pellet. Whether immunosuppression and enhanced PFC levels relate to the same parasite product is not clear as yet, but both effects can be ascribed to a membrane fraction of the parasite.