Down-regulation of human B lymphocyte activities by a Trypanosoma cruzi membrane glycoprotein.
The effects of purified AGC10, a Trypanosoma cruzi membrane glycoprotein, on normal human B lymphocytes were studied in this work. In the presence of AGC10, [3H]-thymidine uptake by human peripheral blood mononuclear cells stimulated with the B cell-specific mitogen SACI (killed Staphylococcus aureus Cowan I) was markedly decreased. This alteration was accompanied by others such as decreased expression of the CD122 and CD132 chains of the IL-2R complex. These inhibitory effects appeared to be somewhat selective, as expression of CD25, another IL-2R chain, was not affected by AGC10 and no significant modification occurred in the expression of the B-cell-specific marker CD19 or CD21. In contrast, AGC10 did reduce the levels of expression of CD86 and CD80, molecules known to play critical roles in B cell interactions with T lymphocytes. Fairly large subpopulations of, but not all, B lymphocytes had their expression of CD122(+), CD132(+), CD86(+) and CD80(+) reduced to undetectable levels in the presence of AGC10. However, the SACI-activated B cells that remained capable of expressing these molecules in the presence of AGC10 did so at normal levels. This was denoted by comparable mean fluorescence intensity values representing the expression of CD122, CD132, CD86 or CD80 molecules on the surface of SACI-stimulated CD19(+) cells cultured without or with AGC10. These results indicated that AGC10, derived from an organism that causes immunosuppression in infected hosts, down-regulates B cell activities and suggested that the relevant mechanism could involve the molecular alterations described above.
Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824, USA. kierszen@pilot.msu.edu
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D000293:Adolescent; D000328:Adult; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D018941:Antigens, CD19 / Q000378:metabolism; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen; D015536:Down-Regulation; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism / Q000494:pharmacology* / Q000502:physiology; D008875:Middle Aged; D015800:Protozoan Proteins / Q000494:pharmacology* / Q000502:physiology; D017464:Receptors, Complement 3d / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D014349:Trypanosoma cruzi / Q000254:growth & development / Q000276:immunology / Q000472:pathogenicity*
D015703:Antigens, CD; D018941:Antigens, CD19; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497964:CD86 protein, human; D008562:Membrane Glycoproteins; D015800:Protozoan Proteins; D017464:Receptors, Complement 3d