Differences between CD8 super(+) T cells in lupus-prone (NZB X NZW) F1 mice and healthy (BALB/c X NZW) F1 mice may influence autoimmunity in the lupus model

Immunization with portions of a murine antibody to DNA induced Ig peptide- reactive peripheral CD8 super(+) inhibitory T (Ti) cells in non-autoimmune (BALB/c X NZW) F1 (CWF1) mice. Those Ti suppressed in vitro production of IgG anti-DNA by lymphocytes from MHC-matched, lupus-prone (NZB X NZW) F1 (BWF1) mice, primarily via secretion of transforming growth factor- beta (TGF- beta ). However, splenic CD8 super(+) cells from immunized BWF1 mice failed to suppress anti-DNA. Therefore, BWF1 mice were studied for defects in peripheral CD8 super(+) T cells. The potential to suppress autoimmunity mediated by activated CD4 super(+) helper T and B cells in BWF1 mice was assessed. As BWF1 mice aged, peripheral CD8 super(+) T cells expanded little; fewer than 10% displayed surface markers of activation and memory. In contrast, quantities of splenic CD4 super(+) T and B cells increased; high proportions displayed activation/memory markers. In old compared to young BWF1 mice, splenic cell secretion of two cytokines required for generation of CD8 super(+) T effectors, IL-2 and TGF- beta , was decreased. Immunizing BWF1 mice activated peptide-reactive CD8 super(+) T cells, but their number was decreased compared to young BWF1 or old normal mice. While peptide- reactive splenic CD8 super(+) T cells from immunized BWF1 mice did not survive in short-term cultures, similar CD8 super(+) T cell lines from immunized CWF1 mice expanded and on transfer into BWF1 mice delayed autoimmunity and prolonged survival. Therefore, CD8 super(+) T cells in old BWF1 mice are impaired in expansion, acquisition of memory, secretion of cytokine, and suppression of autoimmunity. Understanding these defects might identify targets for therapy in systemic lupus erythematosus.