A1/Bfl-1 expression is restricted to TCR engagement in T lymphocytes.
We analyzed regulation of the prosurvival Bcl-2 homologue A1, following T-cell receptor (TCR) or cytokine receptor engagement. Activation of CD4(+) or CD8(+) T cells by antigenic peptides induced an early but transient IL-2-independent expression of A1 and Bcl-xl mRNA and proteins, whereas expression of Bcl-2 was delayed and required IL-2. Cytokines such as IL-2, IL-4, IL-7 or IL-15 prevented apoptosis of activated T cells that effect being associated with the maintenance of Bcl-2, but not of A1 expression. However, restimulation of activated or posteffector T cells with antigenic peptide strongly upregulated A1 mRNA and maintained A1 protein expression. IL-4, IL-7 or IL-15 also prevented cell death of naive T cells. In those cells, cytokines upregulated Bcl-2, but not A1 expression. Therefore, in naive, activated and posteffector T cells, expression of A1 is dependent on TCR but not on cytokine receptor engagement, indicating that A1 is differently regulated from Bcl-xl and Bcl-2.
Verschelde
C
C
Laboratoire d'immuno-pharmacologie, INSERM U503, Centre d'ètude et de Recherche en Virologie. et Immunologie, Lyon, France.
Walzer
T
T
Galia
P
P
Biémont
M-C
MC
Quemeneur
L
L
Revillard
J-P
JP
Marvel
J
J
Bonnefoy-Berard
N
N
D000818:Animals; D000941:Antigens / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D015870:Gene Expression; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D015778:Minor Histocompatibility Antigens; D010455:Peptides / Q000276:immunology; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D018121:Receptors, Cytokine / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*
D000941:Antigens; C096816:BCL2-related protein A1; D016207:Cytokines; D015778:Minor Histocompatibility Antigens; D010455:Peptides; D020033:Protein Isoforms; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D018121:Receptors, Cytokine