CD8 functions as an inhibitory ligand in mediating the immunoregulatory activity of CD8+ cells.
Antisense and sense transfection technologies were employed in cellular coculture systems to investigate the physiologic requirements for CD8-dependent immunoregulation. Our data indicate that cells bearing genetically engineered CD8 molecules incorporating a glycoinositolphospholipid membrane anchor, as well as fixed cells bearing natural CD8 molecules, retain specific, CD8-dependent immunoregulatory activity. These findings together support the novel concept that CD8, a molecule traditionally thought of as a receptor, can function as an inhibitory ligand. CD8-dependent inhibition was shown to induce nonresponsiveness, persisting for at least 24 h, in Ag-specific responders. Moreover, only cells undergoing primary, but not secondary, antigenic stimulation through their TCR were found to be susceptible to CD8-dependent inhibition. Both CD4+ and CD8+ responding T cells were inhibited by CD8+ modulatory cells. These functional analyses of inhibitory and responder cells in CD8-dependent inhibition lay the groundwork for developing artificial CD8-based immunomodulatory peptides and deciphering CD8's role in natural immunoregulation.
Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106.
J E
JE
Hambor
D R
DR
Kaplan
M L
ML
Tykocinski
D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000502:physiology*; D016827:CD8 Antigens; D002460:Cell Line; D015870:Gene Expression; D006801:Humans; D007108:Immune Tolerance; D008024:Ligands; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000502:physiology / Q000648:ultrastructure; D012313:RNA; D016372:RNA, Antisense; D011994:Recombinant Proteins; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors; D014162:Transfection
D000945:Antigens, Differentiation, T-Lymphocyte; D016827:CD8 Antigens; D008024:Ligands; D008562:Membrane Glycoproteins; D016372:RNA, Antisense; D011994:Recombinant Proteins; D012313:RNA