L-canavanine acts on suppressor-inducer T cells to regulate antibody synthesis: lymphocytes of systemic lupus erythematosus patients are specifically unresponsive to L-canavanine

L-Canavanine (LC) is an amino acid contained in alfalfa seeds that provokes a disease state similar to systemic lupus erythematosus (SLE) in primates. In vitro experiments showed that LC stimulated proliferation of human phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMC) and T cells of healthy donors but not of pokeweed mitogen (PWM)-stimulated PBMC. LC inhibited spontaneous generation of immunoglobulin-secreting cells (ISC) of PBMC, while it enhanced ISC generation of CD8(-) cells. LC inhibited PWM-induced ISC generation of CD8(-) cells but not of CD4(-) cells, indicating that LC stimulates CD8(-) cells more strongly than CD4(-) cells. The stimulation index of lymphocyte proliferation (PHA + LC/PHA) was greater in CD8(-)Leu8(+) cells than CD8(-)Leu8(-) cells. The stimulation index was also higher in PBMC than in PBMC plus CD8(-)Leu8(-) cells, the former population containing relatively increased CD8(-)Leu8(+) cells. These findings suggest that LC acts mainly on CD8(-)Leu8(+) cells. That LC acts on CD8(-)Leu8(+) cells was confirmed by the finding that LC inhibited ISC generation of non-T plus CD4(+)Leu8(+), but not of non-T plus CD8(-)Leu8(-) cells. In addition, we found that PBMC of SLE patients were specifically unresponsive to LC stimulation. The stimulation index of lymphocyte proliferation (PHA + LC/PHA) in SLE patients (n = 16) was 0.97 +/- 0.19, whereas that in age-matched healthy control (n = 17) was 1.45 +/- 0.40 (P less than 0.001). Patients with active disease were especially unresponsive to LC. Its responsiveness did not correlate with the dose of prednisolone administered. These findings suggest that the lymphocyte response to LC depends primarily on the existence of functional CD8(-)Leu8(+) cells. Moreover, it appears that suppressor-inducer T cells, responsive to LC, are especially deficient in SLE.