Innate immunity together with duration of antigen persistence regulate effector T cell induction.
Proliferation of T cells is important for the expansion of specific T cell clones during immune responses. In addition, for the establishment of protective immunity against viruses, bacteria, and tumors, the expanded T cells must differentiate into effector T cells. Here we show that effector T cell generation is driven by activation of APCs and duration of antigenic stimulation. Adoptively transferred TCR-transgenic T cells extensively proliferated upon immunization. However, these T cells failed to differentiate into effector cells and died within 1 wk after immunization unless antigenic peptides persisted for >1 day or were presented by activated APCs. The induction of protective immunity in a nontransgenic system was more stringent, since activation of APCs or prolonged Ag persistence alone was not sufficient to drive immunity. In contrast, Ag had to be presented for several days by activated APCs to trigger protective T cell responses. Thus, activation of APCs and duration of Ag presentation together regulate the induction of protective T cell responses.
Storni
Tazio
T
Cytos Biotechnology, Schlieren-Zurich, Switzerland.
Ruedl
Christiane
C
Renner
Wolfgang A
WA
Bachmann
Martin F
MF
D000818:Animals; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology*; D015703:Antigens, CD / Q000096:biosynthesis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D000956:Antigens, Viral / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism; D015415:Biomarkers / Q000032:analysis; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D005260:Female; D006023:Glycoproteins / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism; D018960:Hyaluronan Receptors / Q000096:biosynthesis; D007113:Immunity, Innate / Q000235:genetics; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000235:genetics; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D013997:Time Factors; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology; D014764:Viral Proteins / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism; D014771:Virion / Q000276:immunology / Q000378:metabolism; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D000956:Antigens, Viral; D015415:Biomarkers; D006023:Glycoproteins; D018960:Hyaluronan Receptors; D037181:Lectins, C-Type; D010446:Peptide Fragments; D015375:Receptors, Interleukin-2; D014764:Viral Proteins; D014765:Viral Vaccines; D000099192:CD69 Antigens; C094244:glycoprotein peptide 33-41, Lymphocytic choriomeningitis virus