Rapid development of Th2 activity during T cell priming.
The paradigm of T helper-1 (Th-1) and Th-2 cells developing from non-committed naive precursors is firmly established. Th1 cells are characterized by IFNgamma production and, in mice, the selective switching to IgG2a. Conversely IL-4 production and selective switching to IgG1 and IgE characterize Th2 cells. Analysis of Th2 induction in vitro indicates that this polarization develops gradually in T cells activated by anti-CD3 in the presence of IL-4; conversely anti-CD3 and IFNgamma induce Th1 cells. In this report, we explore evidence that indicates that the T helper cell polarization in vivo cannot solely be explained by the cytokine environment. This is provided by studying the early acquisition of Th1 and Th2 activities during responses to a mixture of Th1 and Th2-inducing antigens. It is shown that these divergent forms of T cell help can rapidly develop in cells within a single lymph node. It is argued that early polarization to show Th-1 or Th-2 behavior can be induced by signals delivered during cognate interaction between virgin T cells and dendritic cells, in the absence of type 1 or type 2 cytokines. This contrasts with the critical role of the cytokines in reinforcing the Th-phenotype and selectively expanding T helper clones.
University of Birmingham, Medical Research Council Centre for Immune Regulation, Birmingham B15 2TT, UK.
Adam F
AF
Cunningham
Kai-Michael
KM
Toellner
D000276:Adjuvants, Immunologic; D000818:Animals; D000911:Antibodies, Monoclonal; D001973:Bromodeoxyuridine / Q000097:blood / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D007114:Immunization; D007072:Immunoglobulin D / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D009596:Nitrophenols / Q000276:immunology; D010567:Pertussis Vaccine / Q000276:immunology; D010648:Phenylacetates; D012333:RNA, Messenger / Q000032:analysis / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D005719:gamma-Globulins / Q000276:immunology
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D007072:Immunoglobulin D; D007074:Immunoglobulin G; D009596:Nitrophenols; D010567:Pertussis Vaccine; D010648:Phenylacetates; D012333:RNA, Messenger; D005719:gamma-Globulins; C026242:4-hydroxy-5-nitrophenyl acetic acid; D015847:Interleukin-4; D007371:Interferon-gamma; D001973:Bromodeoxyuridine