Differences between CD8+ 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+ 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+ cells from immunized BWF1 mice failed to suppress anti-DNA. Therefore, BWF1 mice were studied for defects in peripheral CD8+ T cells. The potential to suppress autoimmunity mediated by activated CD4+ helper T and B cells in BWF1 mice was assessed. As BWF1 mice aged, peripheral CD8+ T cells expanded little; fewer than 10% displayed surface markers of activation and memory. In contrast, quantities of splenic CD4+ 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+ T effectors, IL-2 and TGF-beta, was decreased. Immunizing BWF1 mice activated peptide-reactive CD8+ T cells, but their number was decreased compared to young BWF1 or old normal mice. While peptide-reactive splenic CD8+ T cells from immunized BWF1 mice did not survive in short-term cultures, similar CD8+ T cell lines from immunized CWF1 mice expanded and on transfer into BWF1 mice delayed autoimmunity and prolonged survival. Therefore, CD8+ 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.
Rheumatology, Harbor/UCLA Medical Center, Torrance, USA.
George A
GA
Karpouzas
Antonio
A
La Cava
Fanny M
FM
Ebling
Ram Raj
RR
Singh
Bevra H
BH
Hahn
D000818:Animals; D017209:Apoptosis; D001323:Autoantibodies / Q000096:biosynthesis; D015551:Autoimmunity; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D007114:Immunization; D007156:Immunologic Memory; D007376:Interleukin-2 / Q000032:analysis; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008814:Mice, Inbred NZB; D016212:Transforming Growth Factor beta / Q000032:analysis; D053773:Transforming Growth Factor beta1
D001323:Autoantibodies; D007376:Interleukin-2; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1