Repeated antigen exposure is necessary for the differentiation, but not the initial proliferation, of naive CD4(+) T cells.
The mechanisms that regulate CD4(+) T cells responses in vivo are still poorly understood. We show here that initial Ag stimulation induces in CD4(+) T cells a program of proliferation that can develop, for at least seven cycles of division, in the absence of subsequent Ag or cytokine requirement. Thereafter, proliferation stops but can be reinitiated by novel Ag stimulation. This initial Ag stimulation does not however suffice to induce the differentiation of naive CD4(+) T cells into effector Th1 cells which requires multiple contacts with Ag-loaded APC. Thus, recurrent exposure to both Ag and polarizing cytokines appears to be essential for the differentiation of IFN-gamma-producing cells. Ag and cytokine availability therefore greatly limits the differentiation, but not the initial proliferation, of CD4(+) T cells into IFN-gamma-producing cells.
Bajénoff
Marc
M
Center d'Immunologie de Marseille Luminy, Institut National de la Santé et de la Recherche Médicale/Centre National de la Recherche Scientifique/Université de la Méditérranée, Parc Scientifique de Luminy, Marseille, France.
Wurtz
Olivier
O
Guerder
Sylvie
S
D000818:Animals; D000941:Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D005434:Flow Cytometry; D007700:Kinetics; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D009113:Muramidase / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology*; D012333:RNA, Messenger / Q000096:biosynthesis; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction; D020825:T-Box Domain Proteins; D018417:Th1 Cells / Q000276:immunology; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D015533:Transcriptional Activation; D000098815:T-bet Transcription Factor
D000941:Antigens; D016207:Cytokines; D010446:Peptide Fragments; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D014157:Transcription Factors; C066759:hen egg lysozyme peptide (46-61); D009113:Muramidase