Antigen-induced Erk1/2 activation regulates Ets-1-mediated sensitization of CD8+ T cells for IL-12 responses.
The presence of IL-12 during antigen stimulation instructs naive CD8+ T cells for long-term effector responses, but their mechanisms of collaboration are not understood completely. Herein, we report that CD8+ T cells (OT-I T cells) stimulated with antigen for a longer duration show enhanced sensitization to IL-12 as a result of Erk1/2-dependent, increased Ets-1 phosphorylation and subsequent increases in IL-12Rbeta2 expression. Correspondingly, naive OT-I T cells stimulated by antigen for a longer duration in the presence of IL-12, irrespective of frequency of APCs, show robust effector maturation and mount long-term antigen-recall responses upon adoptive transfer. These results identify the role of antigen strength-dependent Erk1/2 activation for Ets-1-mediated collaboration with IL-12 in CD8+ T cells.
Li
Qingsheng
Q
Department of Immunology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Eppolito
Cheryl
C
Odunsi
Kunle
K
Shrikant
Protul A
PA
D000818:Animals; D000941:Antigens / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology* / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D050784:Proto-Oncogene Protein c-ets-1 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D053707:Receptors, Interleukin-12
D000941:Antigens; C494042:Ets1 protein, mouse; C508443:Il12rb2 protein, mouse; D050784:Proto-Oncogene Protein c-ets-1; D053707:Receptors, Interleukin-12; D018664:Interleukin-12; C535148:Mapk1 protein, mouse; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3