T-cell activation and the development of an apoptosis-resistant CD45RO+ T-cell population.
Growing experimental evidence supports a broadening role for the caspases; not only do they participate in the process of apoptosis but also in the control of the cell cycle and cellular proliferation. The biological role of the caspases in the process of T-cell activation and proliferation is still not defined. In the present study, we propose a potential role, by demonstrating an association of T-cell receptor-mediated caspase activity with the development of an apoptosis-resistant memory CD45RO+ T-cell population. As previously shown by us, a time-dependent induction of caspase activity, in the absence of apoptosis, can be observed in CD3-stimulated human peripheral blood lymphocytes. We here show that a population of CD45RO+ cells, with activated caspase-3 and with resistance to tributyltin-induced apoptosis, develops after 3 days of stimulation. A concomitant expression of the anti-apoptotic protein Bcl-xL accompanied the caspase activity and the development of the apoptosis-resistant phenotype. Finally, upon co-culturing with dexamethasone (DEX), the CD3-induced caspase-3 activity was blocked. During this condition, the expression of the activation marker HLA-DR as well as the cellular proliferative response was strongly suppressed. The development of memory cells with a CD45RO+ phenotype was also blocked. Our data support the hypothesis that caspase-3 activity, observed in CD3-stimulated cells, may be an important component in the proliferation process and, furthermore, might play a role for the development of memory T cells, and DEX inhibits this process.
Müller
M
M
Department of Medicine, Division of Respiratory Medicine, Karolinska Institutet, Stockholm, Sweden. malin.muller@ks.se
Grunewald
J
J
Gigliotti
D
D
Eklund
A
A
Stridh
H
H
D017209:Apoptosis / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology; D020169:Caspases / Q000276:immunology; D003907:Dexamethasone / Q000494:pharmacology; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000276:immunology*; D005938:Glucocorticoids / Q000494:pharmacology; D006684:HLA-DR Antigens / Q000494:pharmacology; D006801:Humans; D007156:Immunologic Memory; D017493:Leukocyte Common Antigens / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014220:Trialkyltin Compounds / Q000276:immunology; D051020:bcl-X Protein
C494811:BCL2L1 protein, human; D017252:CD3 Complex; D005938:Glucocorticoids; D006684:HLA-DR Antigens; D019253:Proto-Oncogene Proteins c-bcl-2; D011948:Receptors, Antigen, T-Cell; D014220:Trialkyltin Compounds; D051020:bcl-X Protein; C011559:tributyltin; D003907:Dexamethasone; D017493:Leukocyte Common Antigens; D020169:Caspases