Trypanosomal immunosuppressive factor: a secretion product(s) of Trypanosoma cruzi that inhibits proliferation and IL-2 receptor expression by activated human peripheral blood mononuclear cells.
Coculture of blood forms of Trypanosoma cruzi with human PMBC suppresses the expression of several molecules involved in lymphocyte activation, including receptors for IL-2. Our work was initially undertaken to establish whether this effect required physical parasite-PBMC contact or was mediated by a T. cruzi secretion product. Using culture inserts with cell-impermeable membranes, we were able to demonstrate significant suppression of PHA-induced lymphoproliferation whether the trypanosomes were placed in the same compartment as, or separated from, the PBMC. Similar effects were observed by using supernatants from T. cruzi suspensions. These supernatants, which we refer to as trypanosomal immunosuppressive factor, also inhibited IL-2R expression in response to PHA stimulation. The suppressive effect of the secretion product(s) of T. cruzi was reversible, as evidenced by significant recovery of the proliferative capacity of PBMC after removal of the parasite-containing inserts. Moreover, the extent of the suppression produced by trypanosomal immunosuppressive factor subsided as culture time increased. Treatment of trypanosomal immunosuppressive factor with proteases abrogated its suppressive activity, suggesting that the relevant principle(s) was of protein nature. From ultrafiltration experiments, the molecular mass of the suppressive molecule(s) was estimated to be between 30,000 and 100,000 Da. These results demonstrate for the first time the capacity of T. cruzi to spontaneously secrete a factor that suppresses human lymphocyte responses in vitro. This factor, which may play a role in the down-regulation of host immune function observed in acute chagasic patients, might be a useful tool in exploring the mechanisms that regulate the expression of IL-2R and other surface molecules playing key roles in lymphocyte activation.
Kierszenbaum
F
F
Department of Microbiology and Public Health, Michigan State University, East Lansing 48824.
Cuna
W R
WR
Beltz
L A
LA
Sztein
M B
MB
D000818:Animals; D002478:Cells, Cultured; D006801:Humans; D066298:In Vitro Techniques; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008213:Lymphocyte Activation; D008970:Molecular Weight; D010447:Peptide Hydrolases / Q000494:pharmacology; D010835:Phytohemagglutinins / Q000494:pharmacology; D015375:Receptors, Interleukin-2 / Q000378:metabolism*; D013491:Suppressor Factors, Immunologic / Q000276:immunology; D014349:Trypanosoma cruzi / Q000276:immunology*
D010835:Phytohemagglutinins; D015375:Receptors, Interleukin-2; D013491:Suppressor Factors, Immunologic; D010447:Peptide Hydrolases