Immunoregulatory CD8⁺ cells recognize antigen-activated CD4⁺ cells in myasthenia gravis patients and in healthy controls

CD8⁺ cells inhibiting the response of CD4⁺ cells exist in rodents, recognizing epitopes unique to a CD4⁺ clone (Ids) or expressed by all activated CD4⁺ cell (ergotypes). Stimulation of CD8⁺ cells recognizing ergotypes shared by all Ag-activated CD4⁺ cells would be useful for treatment of diseases involving undesirable CD4⁺ responses to ill defined Ags, such as many autoimmune diseases and allergies. As a first step toward demonstrating the existence of antiergotype 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 receptor, 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 responded vigorously to autologous Ag-activated CD4⁺ cells. The CD8⁺ lines responded equally well to the Ag-activated CD4⁺ cells of different Ag specificity, suggesting that they recognized CD4⁺ ergotypes. They did not seem to respond to CD4⁺ cells activated by PHA. The CD8⁺ cells recognized class I- restricted epitopes, as their response to activated CD4⁺ cells was suppressed by anti-class I Ab. CD8⁺ cells recognizing Ag-activated CD4⁺ were present cells in the controls for 5 to 12 wk after immunization. In myasthenic patients, CD8⁺ cells recognizing activated anti-acetylcholine receptor CD4⁺ cells seemed to be always present.