The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1998/7/297/ $5.00
The Journal of Experimental Medicine, Volume 188, Number 2, July 20, 1998 297-304

Articles

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

Sarah Flynn, Kai-Michael Toellner, Chandra Raykundalia, Margaret Goodall, and Peter Lane

From the Department of Immunology, Birmingham Medical School, Birmingham B15 2TT, United Kingdom

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.

Key Words: Th1–Th2 differentiation • OX40/OX40 ligand • cytokine • T cell priming • cognate B cell–T cell interaction

Address correspondence to Peter Lane, Department of Immunology, Birmingham Medical School, Vincent Dr., Birmingham B15 2TT, UK. Phone: 44-121-4144078; Fax: 44-121-4143599; E-mail: p.j.l.lane{at}bham.ac.uk

Abbreviations used: DC, dendritic cell(s); h, human; L, ligand; m, murine; MMTV, Swiss-type mouse mammary tumor virus; NP-C{gamma}G, (4-hydroxy-3-nitrophenyl) acetyl–chicken {gamma} globulin; RT, reverse transcription.


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