CD4+CD3− Accessory Cells Costimulate Primed CD4 T Cells through OX40 and CD30 at Sites Where T Cells Collaborate with B Cells

In this report we identify an accessory cell that interacts with primed and memory T cells at sites where they collaborate with B cells. These cells are distinguished from conventional dendritic cells by their lack of response to Flt3 ligand and their inability to process antigen. Unlike dendritic cells, the CD4+CD3− cells have little CD80 or CD86 expression but do express high levels of the TNF ligands, OX40 ligand and CD30 ligand. We show that Th2-primed cells express the receptors for these TNF ligands and preferentially survive when cocultured with these cells. Furthermore, we show that the preferential survival of OX40+ T cells and support of memory T cell help for B cells are linked to their association with CD4+CD3− cells in vivo.

Introduction

The generation of antibody responses to protein antigens requires the rapid expansion of generally rare antigen-specific CD4 T cells and their recruitment to the two principle sites where they collaborate with B cells. In the T zone they provide help for B cells, enabling the rapid generation of primary nonsomatically mutated plasma cells in extrafollicular foci Jacob et al. 1991, Liu et al. 1991. In B follicles CD4 T cells initiate the development of germinal centers (GCs), which subsequently give rise to the precursors of long-lived plasma cells Ho et al. 1986, Slifka et al. 1998. Furthermore, following reexposure to antigen, primed memory CD4 T cells provide help to both memory and naive B cells for accelerat