Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Flynn, S. et al.

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.[1]

References

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. Flynn, S., Toellner, K.M., Raykundalia, C., Goodall, M., Lane, P. J. Exp. Med. (1998) [Pubmed]

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