CD4 T cell cytokine differentiation: the B cell activation molecule, OX40 ligand, instructs CD4 T cells to express interleukin 4 and upregulates expression of the chemokine receptor, Blr-1.
This report investigates the role of OX40 ligand (OX40L) and its receptor, OX40, expressed on activated B and T cells, respectively, in promoting the differentiation of T helper type 2 (Th2) CD4 T cells. These molecules are expressed in vivo by day 2 after priming with T cell- dependent antigens. Their expression coincides with the appearance of immunoglobulin (Ig)G switch transcripts and mRNA for interleukin (IL)-4 and interferon (IFN)-gamma, suggesting that this molecular interaction plays a role in early cognate interactions between B and T cells. In vitro, we report that costimulation of naive, CD62Lhigh CD4 T cells through OX40 promotes IL-4 expression and upregulates mRNA for the chemokine receptor, blr-1, whose ligand is expressed in B follicles and attracts lymphocytes to this location. Furthermore, T cell stimulation through OX40 inhibits IFN-gamma expression in both CD8 T cells and IL-12-stimulated CD4 T cells. Although this signal initiates IL-4 expression, IL-4 itself is strongly synergistic. Our data suggest that OX40L on antigen-activated B cells instructs naive T cells to differentiate into Th2 cells and migrate into B follicles, where T cell-dependent germinal centers develop.
Department of Immunology, Birmingham Medical School, Birmingham B15 2TT, United Kingdom.
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Flynn
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Toellner
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Raykundalia
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Goodall
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Lane
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D015847:Interleukin-4 / Q000096:biosynthesis / Q000276:immunology*; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation / Q000276:immunology*; D008562:Membrane Glycoproteins; D051379:Mice; D053278:OX40 Ligand; D019707:Receptors, Chemokine / Q000096:biosynthesis / Q000276:immunology*; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology*; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology; D048069:Tumor Necrosis Factors
D008562:Membrane Glycoproteins; D053278:OX40 Ligand; D019707:Receptors, Chemokine; D018124:Receptors, Tumor Necrosis Factor; C504586:Tnfsf4 protein, mouse; D048069:Tumor Necrosis Factors; D015847:Interleukin-4