EFFECT OF LONG-TERM ANTI-CD4 OR ANTI-CD8 TREATMENT ON THE DEVELOPMENT OF LPC CD4(-) CD8(-) DOUBLE-NEGATIVE T-CELLS AND OF THE AUTOIMMUNE SYNDROME IN MRL-LPR/LPR MICE

We have determined the effect of anti-CD4 or anti-CD8 monoclonal antibody (mAb) treatment from birth on the generation of the Epr CD4(-) CD8(-) double-negative (DN) T cell subset and on the development of lupus-like autoimmune syndrome in MRL-lprllpr mice. Both anti-CD4 and anti-CDS mAb treatments resulted in a marked inhibition of lymphadenopathy, whereas the development of the lpr DN T cells and of the lupus-like autoimmune syndrome strikingly differed in these two groups of mice. The treatment with anti-CD8 mAb almost completely blocked the appearance of the lpr DN T cells without any significant effect on the development of lupus-like autoimmune syndrome in MRL-lprllpr mice. In contrast, mice treated with anti-CD4 mAb failed to develop a lupus-like syndrome, while they still developed the lpr DN T cell subset, the predominant population in their lymph nodes, although absolute numbers were markedly diminished. Our results support the idea that CD8(+) T cells are a major source of the lpr DN T cells, and that the lpr DN T cells play a minor, if any, role in the pathogenesis of lupus-like autoimmune syndrome in MRL-lprllpr mice.