Trypanosoma cruzi reduces the number of high-affinity IL-2 receptors on activated human lymphocytes by suppressing the expression of the p55 and p70 receptor components.
We previously established that Trypanosoma cruzi, the causative agent of Chagas' disease, has the ability to suppress expression of the p55 component of the IL-2R by activated human PBMC. We explored in this work whether the parasite alters the expression of high affinity IL-2R, responsible for the internalization of IL-2 and signal transduction. Radiobinding measurements revealed that the trypanosome indeed inhibited the expression of high affinity IL-2R. Thus, a considerably smaller number of 125I-IL-2 molecules was necessary to saturate the IL-2R on PHA-stimulated PBMC cocultured with T. cruzi than those of control PBMC that had not been exposed to the organisms. Scatchard analysis of equilibrium binding data showed that, in the presence of T. cruzi, the number of high affinity IL-2R per cell was reduced by approximately 80%. The Kd for IL-2 binding to the fewer IL-2R expressed on PBMC exposed to T. cruzi was not significantly different from that of IL-2R on nonsuppressed PBMC. Independent measurements made after cross-linking 125I-IL-2 to its specific receptors with disuccinimidylsuberate showed that both the p55 and p70 components of the IL-2R were markedly suppressed and to comparable extents. These results demonstrate for the first time that T. cruzi suppresses the expression of high affinity IL-2R by human cells, including the p70 chain of the heterodimeric IL-2R. It is noteworthy that the in vitro model system we used in this work to study the mechanisms whereby T. cruzi may induce the immunosuppression that accompanies acute Chagas' disease also lends itself to the exploration of the regulatory mechanisms governing the expression of IL-2R by human PBMC.
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; D003432:Cross-Linking Reagents; D006801:Humans; D007165:Immunosuppression Therapy; D008213:Lymphocyte Activation; D008970:Molecular Weight; D011487:Protein Conformation; D011869:Radioligand Assay; D015375:Receptors, Interleukin-2 / Q000302:isolation & purification / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000469:parasitology; D013936:Thymidine / Q000378:metabolism; D014349:Trypanosoma cruzi / Q000276:immunology*
D003432:Cross-Linking Reagents; D015375:Receptors, Interleukin-2; D013936:Thymidine