Immunoglobulin Production Induced by CD57+GC-Derived Helper T Cellsin VitroRequires Addition of Exogenous IL-2

Abstract

Germinal centers (GC) are well-defined areas in lymphoid organs were B cells proliferate and differentiate in response to T-cell-dependent antigens. The GC comprises B cells, follicular dendritic cells, tangible body macrophages, and a low number of CD4+T cells. A large portion of these T cells expresses CD57. We have examined the ability of the CD4+CD57+GC T cells to become activated and to take part in B cell activation processes. These T cells coexpress CD45RO, CD69, CD28, and upon mitogenic stimulation CD25. The cell population was found neither to containe nor to be able to produce any specific mRNA for IL-2, IL-4, and IFN-γ upon activation. Levels of mRNA encoding CD40 ligand was also undetectable under similar conditions. Furthermore, in contrast to ordinary CD4+T cells, this population expressing CD57 was unable to induce B cells to Ig production in the presence of pokeweed mitogen or SEA unless IL-2 was added to the cultures. However, despite their apparent lack of function CD4+CD57+GC T cells were found to rescue GC B cells from cell deathin vitroto the same extent as CD4+CD57−Thcells. The phenotypical and functional differences found between these T cells and regular Th-cells suggest that they either represent a T cell subset with distinct properties within the GC yet to be determined or that they represent T cells, late in the immune response, having lost most of their original functions and capabilities.