| Abstract: | Autoimmune MRL-lpr mice have a defect in antigen-specific T-cell proliferation. Our studies indicate that this defect is caused by the massive expansion in MRL-lpr mice of a unique T-cell subset which is unresponsive to antigenic signals. Pharmacologic doses of PGE1 suppress this lymphoid hyperplasia and thus prevent loss of T-cell functions by preventing numeric dilution of normal T cells by defective T cells. The inability of the unique subset of T cells to respond to antigenic signals cannot be corrected by the addition of interleukin 2 (IL-2), implying that additional cellular properties are required to initiate proliferation. While the vast majority of freshly harvested MRL-lpr T cells lack IL-2 receptors (R) as measured by anti-IL-2R monoclonal antibody staining, a large fraction of nonstimulated, cultured (48 hr) MRL-lpr T cells, but not MRL-++ T cells, express IL-2R. These experiments suggest that MRL-lpr cells are activated in vivo but an undefined suppressive influence prevents detection or expression of IL-2R until these cells are explanted and cultured. |
