Abstract
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.
Original language | English |
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Pages (from-to) | 297-304 |
Number of pages | 8 |
Journal | The Journal of Experimental Medicine |
Volume | 188 |
Issue number | 2 |
DOIs | |
Publication status | Published - 20 Jul 1998 |
Keywords
- Animals
- Membrane Glycoproteins
- Cell Differentiation
- Mice
- Tumor Necrosis Factors
- Th2 Cells
- B-Lymphocytes
- Lymphocyte Cooperation
- CD4-Positive T-Lymphocytes
- Receptors, Chemokine
- Lymphocyte Activation
- Interleukin-4
- Receptors, Tumor Necrosis Factor
- Th1 Cells