ANERGIC T-CELLS ACTIVELY SUPPRESS T-CELL RESPONSES VIA THE ANTIGEN-PRESENTING CELL

We here show that anergic T cells are active mediators of T cell suppr ession. In cc-culture experiments, we found that anergic T cells, deri ved from established rat T cell clones and rendered anergic via T cell presentation of the specific antigen (Ag), were active inhibitors of T cell responses. Anergic T cells inhibited not only the responses of T cells with the same Ag specificity as the anergic T cells, but were also capable of efficiently inhibiting polyclonal T cell responses dir ected to other epitopes. This suppression required close cell-cell con tact between antigen-presenting cells (APC), anergic T cells and respo nder T cells, and only occurred when the epitope recognized by the ane rgic T cell was present. The suppression was not caused by passive com petition for ligands on the APC surface, IL-2 consumption, or cytolysi s, and was not mediated by soluble factors derived from anergic T cell s that were stimulated with their specific Ag. When responder T cells were added 24 h after co-culturing anergic cells in the presence of Ag and APC, T cell responses were still suppressed, indicating that the suppressive effect was persistently present. However, anergic T cells were not able to suppress responder T cells that had already received a full activation signal. We propose that suppression by anergic T cel ls is mediated via the APC, either through modulation of the T cell-ac tivating capacity of the APC (APC/T cell interaction), or by inhibitio n of T cells recognizing their ligand in close proximity on the same A PC (T/T cell interaction).