Elevated in vivo and in vitro secretion of CD8-alpha molecules in patients with systemic lupus erythematosus

Endogenously activated CD8+ cells contribute to the aberrant immune regulation that characterizes SLE. Because stimulation of CD8+ cells with lectin/Ag triggers release of CD8-alpha molecules (sCD8), we measured, in patients with SLE, serum sCD8 content, its correlation with disease activity, and the in vitro release of sCD8 by SLE PBMCs. sCD8 levels, measured by ELISA in sera of 50 SLE patients, were higher than normal in 16 out of 21 mildly active and 15 out of 15 active SLE patients. sCD8 correlated positively with the clinical index for disease activity (r = 0.57, p = 0.001) and with sIL-2R levels (r = 0.52, p < 0.0001), and negatively with serum C3 levels (r = -0.5, p < 0.04). Freshly isolated SLE PBMCs had higher than normal CD8-alpha mRNA levels and secreted high levels of sCD8 in vitro (p < 0.05 vs control PBMC). sCD8 in vitro release by SLE PBMCs may be modulated by non-CD8+ cells. Thus, anti-CD2 mAb inhibited sCD8 release, whereas anti-HLA mAb increased it in unseparated PBMCs, but not in CD8+ enriched cultures. Moreover, sCD8 release increased significantly in PBMC cultures enriched for CD8+ DR+ cells by negative selection. Added-back monocytes decreased sCD8 to original levels, but not after glutaraldehyde fixation, nor in the presence of anti-HLA mAb. Further, lectin-induced IgG production and proliferation were reduced in the presence of sCD8, suggesting that the soluble CD8 molecules may be immunoregulatory. Because the high sCD8 levels in sera of active SLE likely reflect pathogenic cell activation, serum CD8 content may be an additional serologic activity marker, and its study could provide insights into mechanisms of disease.