CD4 T-CELL CYTOKINE DIFFERENTIATION - THE B-CELL ACTIVATION MOLECULE,OX40 LIGAND, INSTRUCTS CD4 T-CELLS TO EXPRESS INTERLEUKIN-4 AND UP-REGULATES EXPRESSION OF THE CHEMOKINE RECEPTOR, BLR-1

This report investigates the role of OX40 ligand (OX40L) and its recep tor, OX40, expressed on activated B and T cells, respectively, in prom oting 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-dep endent antigens. Their expression coincides with the appearance of imm unoglobulin (Ig)G switch transcripts and mRNA for interleukin (IL)-4 a nd interferon (IFN)-gamma, suggesting that this molecular interaction plays a role in early cognate interactions between B and T cells. In v itro, we report that costimulation of naive, CD62L(high) CD4 T cells t hrough OX40 promotes IL-4 expression and upregulates mRNA for the chem okine receptor, blr-1, whose ligand is expressed in B follicles and at tracts lymphocytes to this location. Furthermore, T cell stimulation t hrough OX40 inhibits IFN-gamma expression in both CD8 T cells and IL-1 2-stimulated CD4 T cells. Although this signal initiates IL-4 expressi on, IL-4 itself is strongly synergistic. Our data suggest that OX40L o n antigen-activated B cells instructs naive T cells to differentiate i nto Th2 cells and migrate into B follicles, where T cell-dependent ger minal centers develop.