IMMUNOREGULATORY CD8(-ACTIVATED CD4(+) CELLS IN MYASTHENIA-GRAVIS PATIENTS AND IN HEALTHY CONTROLS() CELLS RECOGNIZE ANTIGEN)

CD8(+) cells inhibiting the response of CD4(+) cells exist in rodents, recognizing epitopes unique to a CD4(+) clone (Ids) or expressed by a ll activated CD4(+) cell (ergotypes). Stimulation of CD8(+) cells reco gnizing ergotypes shared by all Ag-activated CD4(+) cells would be use ful for treatment of diseases involving undesirable CD4(+) responses t o ill defined Ags, such as many autoimmune diseases and allergies. As a first step toward demonstrating the existence of anti-ergotype CD8() immunoregulatory cells in humans, we investigated here whether CD8() cells recognizing Ag-activated CD4(+) cells exist in autoimmune and healthy humans. CD4(+) cells specific for human muscle acetylcholine r eceptor, tetanus, or diphtheria toxoids were propagated from patients with myasthenia gravis patients and healthy controls. Ag-activated CD4 (+) cells were irradiated and used as Ag to test the response of CD4()-depleted CD8(+)-enriched PBMC (CD8(+) PBMC) from myasthenic patients and controls and to propagate short-term CD8(+) cell lines from CD8() PBMC. In both patients and controls CD8(+) PBMC and CD8(+) lines res ponded vigorously to autologous Ag-activated CD4(+) cells. The CD8(+) lines responded equally well to the Ag-activated CD4(+) cells of diffe rent Ag specificity, suggesting that they recognized CD4(+) ergotypes. They did not seem to respond to CD4(+) cells activated by PHA. The CD 8(+) cells recognized class I-restricted epitopes, as their response t o activated CD4(+) cells was suppressed by anti-class I Ab. CD8(+) cel ls recognizing Ag-activated CD4(+) were present cells in the controls for 5 to 12 wk after immunization. In myasthenic patients, CD8(+) cell s recognizing activated anti-acetylcholine receptor CD4(+) cells seeme d to be always present.