CD28-mediated activation in CD45RA+ and CD45RO+ T cells: enhanced levels of reactive oxygen intermediates and c-Rel nuclear translocation in CD45RA+ cells.
We have analyzed the effect of complete T cell activation (anti-CD3 plus anti-CD28) on the activation of NF-kappaB in CD45RA+ (naive) and CD45RO+ (memory/effector) T cells. Long exposure (24 h) induced stronger NF-kappaB DNA binding in CD45RA+ cells than in CD45RO+ cells. Analysis of the nuclear c-Rel protein indicated that after anti-CD3+anti-CD28 stimulation the level of c-Rel was higher in CD45RA+ cells. Analysis of the cytoplasmic inhibitor IkappaBalpha indicated that anti-CD3+anti-CD28 stimulation induced a long-lasting degradation in CD45RA+ cells but in CD45RO+ cells the degradation process was more rapid. Because the CD28 costimulus is known to induce the production of reactive oxygen intermediates (ROIs), the intracellular ROI levels in CD45RA+ and CD45RO+ cells were compared by flow cytometry. ROIs were produced in both cell types, but more strongly in CD45RA+ cells. The data presented in this study further emphasize the differences between CD45RA+ and CD45RO+ T lymphocytes in ROI-dependent signaling pathways.
Lahdenpohja
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Department of Microbiology and Immunology, University of Tampere Medical School, Finland. llnila@uta.fi
Hurme
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M
D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D018106:CD28 Antigens / Q000276:immunology*; D002467:Cell Nucleus / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D006801:Humans; D017493:Leukocyte Common Antigens / Q000276:immunology*; D008213:Lymphocyte Activation / Q000502:physiology*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D020569:Proto-Oncogene Proteins c-rel; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013268:Stimulation, Chemical; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D018106:CD28 Antigens; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D020569:Proto-Oncogene Proteins c-rel; D017382:Reactive Oxygen Species; D004247:DNA; D017493:Leukocyte Common Antigens